Mitigating necrosis in transgenic glyphosate-tolerant cotton plants treated with herbicidal glyphosate formulations

ABSTRACT

This invention relates generally to improved methods and herbicidal glyphosate compositions for use in controlling the growth of weeds and unwanted vegetation, and particularly for use in controlling weeds in a crop of transgenic glyphosate-tolerant cotton plants by over-the-top, foliar application of a herbicidal glyphosate formulation.

This application claims the benefit of U.S. provisional application Ser.No. 60/659,001, filed Mar. 4, 2005 and U.S. provisional application Ser.No. 60/713,948, filed Sep. 1, 2005, the entire contents of which areincorporated herein by reference.

BACKGROUND OF THE INVENTION

This invention relates generally to improved methods for controllingweeds in a crop of transgenic glyphosate-tolerant cotton plants byover-the-top, foliar application of a herbicidal glyphosate formulation.The present invention is further directed to herbicidal glyphosatecompositions useful in practicing the weed control methods disclosedherein.

Cotton (i.e., Gossypium hirsutum) provides an ideal fiber for textilemanufacture as well as oil for human consumption, feed for livestock andbase chemicals for a variety of industrial products. Cotton productionis well-established in the United States and many other areas of theworld. As in other cultivated crops, weeds can cause significant yieldlosses and require careful management by the grower as they interferethrough their competition for available resources including water,nutrients and light. In cotton, weeds can also impede harvest and have anegative economic impact on the grower by not only reducing cotton lintyields, but also lint quality. Weed control practices in cotton haveincluded cultural, mechanical, biological and chemical methods. Amongthese, chemical weed control has been widely adopted along with the useof tillage (e.g., seed bed preparation, tillage) and cultural (e.g.,crop rotation, field selection) methods.

N-(phosphonomethyl)glycine, known in the agricultural chemical art asglyphosate, is a highly effective and commercially important broadspectrum phytotoxicant useful in controlling the growth of germinatingseeds, emerging seedlings, maturing and established woody and herbaceousvegetation, and aquatic plants. Glyphosate is used as a post-emergentherbicide to control the growth of a wide variety of annual andperennial grass and broadleaf weed species in cultivated crop lands,including cotton production, and is the active ingredient in the ROUNDUPfamily of herbicides available from Monsanto Company (Saint Louis, Mo.).

Glyphosate and salts thereof are conveniently applied in aqueousherbicidal formulations, usually containing one or more surfactants, tothe foliar tissues (i.e., the leaves or other photosynthesizing organs)of the target plant. After application, the glyphosate is absorbed bythe foliar tissues and translocated throughout the plant. Glyphosatenoncompetitively blocks an important biochemical pathway that is commonto virtually all plants. More specifically, glyphosate inhibits theshikimic acid pathway that leads to the biosynthesis of aromatic aminoacids. Glyphosate inhibits the conversion of phosphoenolpyruvic acid and3-phosphoshikimic acid to 5-enolpyruvyl-3-phosphoshikimic acid byinhibiting the enzyme 5-enolpyruvyl-3-phosphoshikimic acid synthase(EPSP synthase or EPSPS) found in plants.

Advances in genetic engineering have provided the requisite tools totransform cotton and other cultivated plants to contain foreign genesfor improvement of certain agronomic traits and the quality of theproduct. One such trait of particular agronomic and environmentalimportance is herbicide tolerance, in particular, tolerance toglyphosate herbicide. Glyphosate-resistant or tolerant crop plants mayreduce the need for tillage to control weeds, thereby effectivelyreducing soil erosion. Further, glyphosate-tolerant crop plants providegreater simplicity and flexibility in attaining adequate weed control.

Glyphosate-tolerant cotton can be produced, for example, by introducinginto the genome of the plant, the capacity to express various native andvariant plant or bacterial EPSPS enzymes that have a lower affinity forglyphosate and therefore retain their catalytic activity in the presenceof glyphosate (See, for example, U.S. Pat. Nos. 5,633,435, 5,094,945,4,535,060, 6,040,497 and 6,740,488). Glyphosate-tolerance has beenintroduced into cotton plants and is a successful product now widelyused in cotton production. The current commercial ROUNDUP READY cottonevent designated 1445 available from Monsanto Company provides excellentresistance to glyphosate. Glyphosate is typically applied over-the-top(OTT) of ROUNDUP READY cotton from emergence through the four leaf nodestage of development (e.g., at rates of up to about 0.75 poundsglyphosate acid equivalent per acre (lb a.e./A or about 0.84 kga.e./ha). ROUNDUP READY cotton varieties used in combination withROUNDUP glyphosate herbicidal formulations have become the standardprogram for weed management in cotton production in the United States.The primary advantage to growers for using the ROUNDUP READY cottonsystem is that it allows simple and convenient application ofglyphosate, a broad spectrum, post-emergence herbicide, to effectivelycontrol weeds and grasses with excellent crop safety and less dependenceon pre-plant herbicide applications. Other benefits include a better fitinto no-till and reduced tillage systems. ROUNDUP READY cotton hasexpanded the options for weed management and made the practice of weedcontrol much easier, less expensive and more flexible. Growers havereported making fewer trips across fields to apply herbicides as well asmaking fewer cultivation trips, which conserves fuel and reduces soilerosion. Glyphosate-tolerant cotton, therefore, decreases theenvironmental risks posed by herbicides while at the same timeincreasing the efficacy of necessary chemical weed control.

Although widely accepted as a standard in cotton production, ROUNDUPREADY cotton varieties do however impose some limitations on the grower.ROUNDUP READY cotton varieties possess reproductive bodies that aresusceptible to glyphosate-mediated injury that may, in some cases,result in delayed maturity or reproductive injury as measured by flowerpollen shed, flower drop, boll drop, and/or lint yield loss.Accordingly, in order to avoid or minimize such reproductive injury,over-the-top applications of glyphosate herbicides to cotton plantsgrown from seed of ROUNDUP READY cotton event 1445 and progeny thereofare generally discontinued from the fifth leaf node stage and beyond(e.g., through layby) and instead glyphosate is usually applied as apost-directed spray between the crop rows during this period of growthin order to minimize contact with the cotton plants. Directed herbicideapplication requires specialized equipment that is often susceptible tomisapplication, must be operated at lower speeds and requires a greaternumber of trips per acre compared to broadcast applicators.

It is believed that the lack of reproductive glyphosate tolerance thatlimits later stage foliar application of glyphosate to cotton plantscorresponding to ROUNDUP READY cotton event designated 1445 is theresult of insufficient CP4 EPSPS expression in critical tissues, highersensitivity of these tissues to glyphosate, and accumulation of highamounts of glyphosate in those strong sink tissues. Recently, asdisclosed in International Publication No. WO 2004/072235, MonsantoCompany has developed a new glyphosate-tolerant cotton event (designatedMON 88913, to be commercially named ROUNDUP READY FLEX cotton and havingseed deposited with American Type Culture Collection with Accession No.PTA-4854) to provide cotton growers with an improved product formanagement of economically damaging weeds. ROUNDUP READY FLEX cottonprovides an increased margin of fruit retention and crop safety, due toincreased tolerance to glyphosate in reproductive tissues. This allowsfor an expanded window for over-the-top ground application of glyphosateagricultural herbicides (e.g., at rates of up to about 1.125 poundsglyphosate acid equivalent per acre (lb a.e./A or about 1.26 kg a.e./ha)extending from cotton emergence up to layby, the critical timing forweed control in cotton. Through these enhanced treatment opportunities,the grower can more effectively manage weed control in cotton usingover-the-top herbicide applications as compared to post-directed orhooded-sprayer applications.

Despite the widely-recognized advantages in weed control provided byROUNDUP READY and ROUNDUP READY FLEX cotton, it has been observed thatthese transgenic cotton varieties, under certain environmentalconditions, exhibit a susceptibility to leaf tissue necrosis followingover-the-top application of glyphosate herbicides. In the case ofover-the-top application of glyphosate herbicides to ROUNDUP READY FLEXcotton at later stages of plant development, the appearance of necroticlesions on the treated cotton plants may appear to be more pronounceddue to the more fully developed canopy and greater available leaf area.This phenomenon is rare and such leaf injury, if it is encountered atall, is generally limited with little or no further expression of injuryand the cotton plants recover with essentially no yield loss ordeleterious effect on fertility under standard or recommended ROUNDUPtreatment protocols. In particular, the cotton apical growing point andsubsequent leaves appear unaffected.

Accordingly, there exists a need for methods and herbicidal glyphosateformulations useful for over-the-top, foliar application to transgenicglyphosate-tolerant cotton plants that are effective in weed control andconsistently avoid inducing significant leaf necrosis in the treatedplants in the variable environmental conditions that may be encounteredduring the growing season.

SUMMARY OF THE INVENTION

As discussed in detail below, in accordance with the present invention,it has been discovered that the leaf necrosis phenomenon sometimesobserved in transgenic glyphosate-tolerant cotton plants followingover-the-top application of glyphosate herbicides and under certaingrowing conditions is induced, at least in part, byN-(phosphonomethyl)iminodiacetic acid (PMIDA) and/or salts thereof whichare often present at relatively low concentrations in glyphosateherbicidal formulations. The present invention encompasses variousaspects and embodiments directed to strategies for mitigatingPMIDA-induced necrosis in transgenic glyphosate-tolerant cotton plantstreated with herbicidal glyphosate formulations, including methods ofweed control, glyphosate herbicidal compositions and formulations foruse in the practice of such weed control methods as well as methods ofmanufacturing technical grade glyphosate product for use in preparingsuch glyphosate herbicidal compositions and formulations. Although thepresent invention has specific application in mitigating PMIDA-inducednecrosis in transgenic glyphosate-tolerant cotton plants, many aspectsand embodiments of the invention disclosed herein have widerapplication.

Accordingly, in various embodiments, methods are provided forselectively controlling weeds in a field containing a crop of transgenicglyphosate-tolerant cotton plants. The methods comprise applying asufficient amount of a herbicidal glyphosate formulation comprisingN-(phosphonomethyl)glycine or an agronomically acceptable salt thereofto the crop foliage and weeds to control growth of the weeds. In someembodiments, the crop of transgenic glyphosate-tolerant cotton plantshave increased glyphosate tolerance in vegetative and reproductivetissues such that application of the herbicidal glyphosate formulationwhen at least five leaf nodes are present on a cotton plant of the cropdoes not incur significant glyphosate-mediated reproductive injury tothe plant. In one embodiment, the concentration ofN-(phosphonomethyl)iminodiacetic acid and salts thereof present in theglyphosate formulation and the application rate of the herbicidalglyphosate formulation are controlled so as to not induce significantleaf necrosis in the cotton plants.

In another embodiment, the glyphosate formulation comprisesN-(phosphonomethyl)iminodiacetic acid or salt thereof and a safeningagent in a concentration sufficient to inhibit significant leaf necrosisin the crop induced by N-(phosphonomethyl)iminodiacetic acid or saltthereof present in the glyphosate formulation.

In another embodiment, the herbicidal glyphosate formulation applied tothe crop of transgenic glyphosate-tolerant cotton plants comprisesN-(phosphonomethyl)iminodiacetic acid or salt thereof and an adjuvantother than an alkoxylated alkylamine. The adjuvant is present in anamount effective to decrease cell membrane permeability within the cropto decrease cellular uptake of the N-(phosphonomethyl)iminodiacetic acidor salt thereof in the crop treated with the formulation as compared tocrops treated with an application mixture having the same composition asthe formulation except that an alkoxylated alkylamine is substituted forthe adjuvant.

Alternatively, the herbicidal glyphosate formulation comprisesN-(phosphonomethyl)glycine, predominantly in the form of anagronomically acceptable salt thereof selected from the group consistingof alkali metal salts, alkylamine salts and alkanolamine salts ofN-(phosphonomethyl)glycine, N-(phosphonomethyl)iminodiacetic acid orsalt thereof and a safening agent comprising an adjuvant. Theconcentration of the adjuvant in the herbicidal glyphosate formulationis selected such that the rate of transfer ofN-(phosphonomethyl)iminodiacetic acid or salt thereof into the foliartissues of the crop of transgenic glyphosate-tolerant cotton plants issufficiently slow to inhibit significant leaf necrosis in the cropinduced by N-(phosphonomethyl)iminodiacetic acid or salt thereof presentin the glyphosate formulation.

The present invention further provides herbicidal glyphosatecompositions (e.g., spray solutions, tank mixes and concentrates) usefulfor killing or controlling the growth of weeds in a field containing acrop of transgenic glyphosate-tolerant cotton plants as well as in otherweed control applications. In one embodiment, the composition comprisesN-(phosphonomethyl)glycine or an agronomically acceptable salt thereof,N-(phosphonomethyl)iminodiacetic acid or salt thereof, and a safeningagent in a concentration sufficient to inhibit significant leaf necrosisin the crop induced by N-(phosphonomethyl)iminodiacetic acid or saltthereof present in the glyphosate composition. Suitable safening agentsmay be selected from the group consisting of metal ions, antioxidants,humectants, light absorbing compounds, and mixtures thereof.

In another embodiment, the aqueous herbicidal concentrate compositioncomprises at least about 360 grams per liter (on an acid equivalentbasis) of N-(phosphonomethyl)glycine or an agronomically acceptable saltthereof and less than 5 grams per liter (on an acid equivalent basis) ofN-(phosphonomethyl)iminodiacetic acid or salt thereof. The compositionfurther comprises aminomethylphosphonic acid and the weight ratio ofN-(phosphonomethyl)iminodiacetic acid or a salt thereof toaminomethylphosphonic acid is not more than 0.25:1; or the compositionfurther comprises at least one surfactant other than an alkoxylatedalkyl amine or an alkoxylated phosphate ester; or theN-(phosphonomethyl)glycine is present predominantly in the form of thepotassium, dipotassium, monoammonium, diammonium, sodium,monoethanolamine, n-propylamine, ethylamine, ethylenediamine,hexamethylenediamine or trimethylsulfonium salt thereof; or thecomposition further comprises a surfactant component comprising analkoxylated alkylamine and an alkoxylated phosphate ester; or theN-(phosphonomethyl)glycine is present predominantly in the form of theisopropylamine salt thereof.

In another embodiment, the herbicidal glyphosate composition comprisesN-(phosphonomethyl)glycine predominantly in the form of an agronomicallyacceptable salt thereof selected from the group consisting of alkalimetal salts, alkylamine salts and alkanolamine salts ofN-(phosphonomethyl)glycine; N-(phosphonomethyl)iminodiacetic acid orsalt thereof; and a safening agent comprising an adjuvant in aconcentration selected such that the rate of transfer ofN-(phosphonomethyl)iminodiacetic acid or salt thereof into the foliartissues of the crop of transgenic glyphosate-tolerant cotton plants issufficiently slow to inhibit significant leaf necrosis in the cropinduced by N-(phosphonomethyl)iminodiacetic acid or salt thereof presentin the glyphosate formulation.

In another embodiment, the aqueous concentrate herbicidal glyphosatecomposition comprises N-(phosphonomethyl)glycine or an agronomicallyacceptable salt thereof, the concentration of theN-(phosphonomethyl)glycine or an agronomically acceptable salt thereofbeing at least about 360 or more grams per liter on an acid equivalentbasis; N-(phosphonomethyl)iminodiacetic acid or salt thereof; a metalion safening agent that is subject to formation of a complex or saltwith N-(phosphonomethyl)iminodiacetic acid or an anion formed bydeprotonation or partial deprotonation thereof, wherein the molar ratioof metal ions to N-(phosphonomethyl)iminodiacetic acid equivalent is atleast about 0.4:1; and a surfactant component comprising at least onecationic surfactant.

In another embodiment, the aqueous concentrate herbicidal glyphosatecomposition comprises at least about 360 grams per liter (on an acidequivalent basis) of N-(phosphonomethyl)glycine or an agronomicallyacceptable salt thereof; less than 5 grams per liter (on an acidequivalent basis) of N-(phosphonomethyl)iminodiacetic acid or saltthereof; and aminomethylphosphonic acid (acid equivalent), wherein theweight ratio of N-(phosphonomethyl)iminodiacetic acid or a salt thereofto aminomethylphosphonic acid is not more than 0.25:1.

In another embodiment, the aqueous concentrate herbicidal glyphosatecomposition comprises at least about 360 grams per liter (on an acidequivalent basis) of N-(phosphonomethyl)glycine or an agronomicallyacceptable salt thereof, less than about 5 grams per liter (on an acidequivalent basis) of N-(phosphonomethyl)iminodiacetic acid or saltthereof, and at least one surfactant other than an alkoxylated alkylamine or an alkoxylated phosphate ester.

In another embodiment, the aqueous concentrate herbicidal glyphosatecomposition comprises at least about 360 grams per liter (on an acidequivalent basis) of N-(phosphonomethyl)glycine predominantly in theform of the potassium, dipotassium, monoammonium, diammonium, sodium,monoethanolamine, n-propylamine, ethylamine, ethylenediamine,hexamethylenediamine or trimethylsulfonium salt thereof, and less thanabout 5 grams per liter (on an acid equivalent basis) ofN-(phosphonomethyl)iminodiacetic acid or salt thereof.

In another embodiment, the aqueous concentrate herbicidal glyphosatecomposition comprises at least about 360 grams per liter (on an acidequivalent basis) of N-(phosphonomethyl)glycine or an agronomicallyacceptable salt thereof, less than about 5 grams per liter (on an acidequivalent basis) of N-(phosphonomethyl)iminodiacetic acid or saltthereof, and at least one surfactant component comprising an alkoxylatedalkyl amine or an alkoxylated phosphate ester.

In another embodiment, the aqueous concentrate herbicidal glyphosatecomposition comprises at least about 360 grams per liter (on an acidequivalent basis) of N-(phosphonomethyl)glycine predominantly in theform of the isopropylamine salt thereof, and less than about 5 grams perliter (on an acid equivalent basis) of N-(phosphonomethyl)iminodiaceticacid or salt thereof.

In another embodiment, the aqueous concentrate herbicidal glyphosatecomposition comprises at least about 360 grams per liter (on an acidequivalent basis) of N-(phosphonomethyl)glycine or an agronomicallyacceptable salt thereof; less than 0.45 wt. % ofN-(phosphonomethyl)iminodiacetic acid or salt thereof (acid equivalent)on a glyphosate, acid equivalent (a.e.), basis; andaminomethylphosphonic acid, wherein the weight ratio ofN-(phosphonomethyl)iminodiacetic acid or a salt thereof (acidequivalent) to aminomethylphosphonic acid (acid equivalent) is not morethan 0.25:1.

In another embodiment, the aqueous concentrate herbicidal glyphosatecomposition comprises at least about 360 grams per liter (on an acidequivalent basis) of N-(phosphonomethyl)glycine or an agronomicallyacceptable salt thereof, less than about 0.45 wt. % ofN-(phosphonomethyl)iminodiacetic acid or salt thereof (acid equivalent)on an N-(phosphonomethyl)glycine, a.e., basis, and at least onesurfactant other than an alkoxylated alkyl amine or an alkoxylatedphosphate ester.

In another embodiment, the aqueous concentrate herbicidal glyphosatecomposition comprises at least about 360 grams per liter (on an acidequivalent basis) of N-(phosphonomethyl)glycine predominantly in theform of the potassium, dipotassium, monoammonium, diammonium, sodium,monoethanolamine, n-propylamine, ethylamine, ethylenediamine,hexamethylenediamine or trimethylsulfonium salt thereof, and less thanabout 0.45 wt. % (phosphonomethyl)iminodiacetic acid or salt thereof(acid equivalent) on an N-(phosphonomethyl)glycine, a.e., basis.

In another embodiment, the aqueous concentrate herbicidal glyphosatecomposition comprises at least about 360 grams per liter (on an acidequivalent basis) of N-(phosphonomethyl)glycine or an agronomicallyacceptable salt thereof, less than about 0.45 wt. %N-(phosphonomethyl)iminodiacetic acid or salt thereof on anN-(phosphonomethyl)glycine basis, and at least one surfactant componentcomprising an alkoxylated alkyl amine or an alkoxylated phosphate ester.

In another embodiment, the aqueous concentrate herbicidal glyphosatecomposition comprises at least about 360 grams per liter (on an acidequivalent basis) of N-(phosphonomethyl)glycine predominantly in theform of the isopropylamine salt thereof, and less than about 0.45 wt. %N-(phosphonomethyl)iminodiacetic acid or salt thereof (acid equivalent)on an N-(phosphonomethyl)glycine, a.e., basis.

In a further embodiment, the aqueous concentrate herbicidal glyphosatecomposition comprises at least about 360 grams per liter (on an acidequivalent basis) of N-(phosphonomethyl)glycine predominantly in theform of a salt thereof, less than about 0.45 wt. %N-(phosphonomethyl)iminodiacetic acid or salt (acid equivalent), and atleast about 0.02 wt. % glycine or a salt thereof (acid equivalent), theweight percentages being on an acid equivalent basis relative toN-(phosphonomethyl)glycine, a.e.

In a still further embodiment, the aqueous concentrate herbicidalglyphosate composition comprises at least about 360 grams per liter (onan acid equivalent basis) of N-(phosphonomethyl)glycine predominantly inthe form of a salt thereof, the preparation of the compositioncomprising hydrolyzing a dialkyl phosphonate intermediate, theintermediate comprising a carboxylic acid salt of dialkylN-(phosphonomethyl)glycine or otherwise derived from reaction of adialkylphosphite with N-methylolglycine.

The present invention also provides various technical grade glyphosatecompositions useful in the preparation of herbicidal glyphosatecompositions and formulations. In one embodiment the technical gradeglyphosate composition comprises, on a dry basis, at least 95 wt. %N-(phosphonomethyl)glycine acid equivalent, less than 0.15 wt. %N-(phosphonomethyl)iminodiacetic acid or a salt thereof, and a byproductselected from not more than 0.7 wt. %N-formyl-N-(phosphonomethyl)glycine or not more than 0.03 wt. %N-methyliminodiacetic acid.

In accordance with another embodiment, the technical grade glyphosatecomposition comprises at least 90 wt. % N-(phosphonomethyl)glycine acidequivalent, less than 0.6 wt. % N-(phosphonomethyl)iminodiacetic acid ora salt thereof, and aminomethylphosphonic acid, wherein the weight ratioof N-(phosphonomethyl)iminodiacetic acid or a salt thereof toaminomethylphosphonic acid is not more than 0.25:1, the weightpercentages being on a dry basis.

In accordance with another embodiment, the technical grade glyphosatecomposition comprises at least 90 wt. % N-(phosphonomethyl)glycine acidor salt thereof, less than 0.45 wt. % N-(phosphonomethyl)iminodiaceticacid or a salt thereof, and at least 0.02 wt. % glycine or salt thereof,the weight percentages being on a dry acid equivalent basis.

In accordance with a further embodiment, the technical glyphosatecomposition comprises at least 90 wt. % N-(phosphonomethyl)glycine acidequivalent, between about 0.02 wt. % and about 0.25 wt. %N-(phosphonomethyl)iminodiacetic acid or a salt thereof, and a byproductselected from not more than 0.6 wt. %N-formyl-N-(phosphonomethyl)glycine, the weight percentages being on adry acid equivalent basis.

In another embodiment, the glyphosate product is selected from the groupconsisting of a technical grade glyphosate composition comprising atleast about 90 wt. % glyphosate acid and a concentrated aqueous solutioncomprising at least about 360 grams per liter a.e. of an agronomicallyacceptable salt of glyphosate. The composition comprises less than about0.45 wt. % N-(phosphonomethyl)iminodiacetic acid or a salt thereof (acidequivalent), and between about 0.05 and about 2 wt. % glyphosine or asalt thereof (acid equivalent), on a glyphosate, a.e., basis.

The present invention also provides various processes for thepreparation of glyphosate by oxidation ofN-(phosphonomethyl)iminodiacetic acid wherein the glyphosate product hasa low N-(phosphonomethyl)iminodiacetic acid content. In one embodiment,the process comprises contacting an aqueous reaction medium containingN-(phosphonomethyl)iminodiacetic acid with a gas comprising molecularoxygen in the presence of a catalyst for the oxidation; recovering aglyphosate product from glyphosate obtained in the resulting productreaction solution, the recovery of the glyphosate product comprisingseparating such product from an aqueous mixture wherein the ratio oftotal N-(phosphonomethyl)iminodiacetic acid content to total glyphosatecontent is at least 25% greater than the corresponding ratio in theproduct reaction solution, oxygen having been caused to flow through theaqueous reaction medium in the presence of the catalyst to an extentsufficient to reduce the N-(phosphonomethyl)iminodiacetic acid contentof the product reaction solution to a level such that the recoveredglyphosate product has an N-(phosphonomethyl)iminodiacetic acid contentless than about 600 ppm, basis glyphosate; and removing the glyphosateproduct from the process.

In another embodiment, the process comprises contacting an aqueousreaction medium containing N-(phosphonomethyl)iminodiacetic acid with agas comprising molecular oxygen in the presence of a catalyst for theoxidation; recovering a glyphosate product from glyphosate obtained inthe resulting product reaction solution, oxygen having been caused toflow through the aqueous reaction medium in the presence of the catalystto an extent sufficient to reduce the N-(phosphonomethyl)iminodiaceticacid content of the product reaction solution to a level such that therecovered glyphosate product has an N-(phosphonomethyl)iminodiaceticacid content less than about 600 ppm, basis glyphosate; and removing theglyphosate product from the process.

In accordance with another embodiment, the process comprises oxidizingN-(phosphonomethyl)iminodiacetic acid in an aqueous reaction medium toproduce a product reaction solution containing glyphosate and unreactedN-(phosphonomethyl)iminodiacetic acid; recovering glyphosate from theproduct reaction solution in a product form having aN-(phosphonomethyl)iminodiacetic acid content not greater than 600 ppmon a glyphosate basis, the recovery of the product form comprisingcontacting an aqueous solution comprising the product reaction solution,or a solution comprising N-(phosphonomethyl)iminodiacetic acid derivedfrom the product reaction solution, with an anion exchange resin whichhas a selective affinity for N-(phosphonomethyl)iminodiacetic acid inpreference to glyphosate.

In another embodiment, the process comprises oxidizingN-(phosphonomethyl)iminodiacetic acid in an aqueous reaction medium toproduce a product reaction solution containing glyphosate and unreactedN-(phosphonomethyl)iminodiacetic acid; crystallizing glyphosate from acrystallizer feed solution comprising or derived from the productreaction solution; subjecting the resulting slurry of glyphosatecrystals in mother liquor to solid/liquid separation; purging a fractionof the mother liquor for removal of N-(phosphonomethyl)iminodiaceticacid from the process; and recycling another fraction of the motherliquor to a crystallizer in which glyphosate is crystallized from thefeed solution, the volume of the purge fraction relative to the volumeof the recycle fraction being sufficient that the solid glyphosatecrystals separated in the solid/liquid separation step have anN-(phosphonomethyl)iminodiacetic acid content lower than 600 ppm or canbe contacted with an aqueous wash medium to produce a solid glyphosateproduct having such lower N-(phosphonomethyl)iminodiacetic acid content.

In a further embodiment, the process comprises contacting an aqueousmedium containing N-phosphonomethyl-iminodiacetic acid in a primaryreaction system with a gas comprising molecular oxygen in the presenceof a particulate catalyst for the oxidation to produce a product slurrycomprising a product reaction solution comprising glyphosate andunreacted N-(phosphonomethyl)iminodiacetic acid, and having theparticulate catalyst suspended therein; separating the catalyst from thereaction product solution to produce a filtered product reactionsolution; and contacting an aqueous solution comprising the filteredproduct reaction solution, or derived therefrom, with an oxidizing agentin a polishing reaction zone for further conversion ofN-phosphonomethyl-iminodiacetic acid to glyphosate.

In a further embodiment, the process comprises contacting an aqueousreaction medium containing N-(phosphonomethyl)iminodiacetic acid with agas comprising molecular oxygen in the presence of a noble metal oncarbon catalyst, and in the absence of a concentration of a non-noblemetal promoter that would be effective to either retard the oxidation ofN-(phosphonomethyl)iminodiacetic acid or causes the rate of consumptionof oxygen in the oxidation of formaldehyde or formic acid to bematerially increased relative to the rate of consumption of oxygen inthe oxidation of N-(phosphonomethyl)iminodiacetic acid; and maintainingcontact of the reaction medium with gas comprising molecular oxygen fora time sufficient to reduce the N-(phosphonomethyl)iminodiacetic acidcontent of the resulting product reaction solution to not greater than250 ppm.

In a further embodiment, the process comprises oxidizingN-(phosphonomethyl)iminodiacetic acid in an aqueous reaction medium toproduce a product reaction solution containing glyphosate and unreactedN-(phosphonomethyl)iminodiacetic acid; transferring the product reactionsolution to a product recovery process by which a plurality ofglyphosate products are produced; and operating the product recoveryprocess to produce at least two separate glyphosate salt products ofdiffering N-(phosphonomethyl)iminodiacetic acid content, wherein theglyphosate basis N-(phosphonomethyl)iminodiacetic acid content of one ofthe products is less than about 1000 ppm one at least 25% lower than theN-(phosphonomethyl)iminodiacetic acid content of another of theplurality of glyphosate products.

In a still further embodiment, the process comprises contactingN-(phosphonomethyl)iminodiacetic acid with an oxidizing agent in anaqueous reaction medium within an oxidation reaction zone in thepresence of a catalyst for the oxidation, thereby effecting oxidation ofN-(phosphonomethyl)iminodiacetic acid and producing a reaction solutioncomprising glyphosate or another intermediate which can be converted toglyphosate; and further processing the reaction solution to produce aglyphosate product containing not more than about 600 ppmN-(phosphonomethyl)iminodiacetic acid or salt thereof, the oxidation ofN-(phosphonomethyl)iminodiacetic acid in the aqueous reaction mediumbeing continued until the concentration ofN-(phosphonomethyl)iminodiacetic acid in the reaction medium has beenreduced to a terminal concentration such that the further processingyields a not greater than about 600 ppm, basis glyphosate.

The present invention further provides a programmed control scheme foruse in conjunction with the various processes for the preparation ofglyphosate by oxidation of N-(phosphonomethyl)iminodiacetic acid. Suchprocesses further comprise measuring select process variables whichaffect the N-(methylphosphonic)iminodiacetic acid content of one or moreglyphosate products as produced by the process; controlling the selectprocess variables via automated control loops to conform to set pointsrespectively established in the control loops; transmitting signals tothe programmed controller conveying the values of the measurements andthe set points; computing adjustments to the set points in response tothe signals in accordance with an algorithm inscribed in software withwhich the controller is programmed; and transmitting signals from theprogrammed controller to the control loops for adjustment of the setpoint to conform operation of the process to the algorithm.

The present invention further provides a process for the preparation ofan aqueous herbicidal concentrate composition comprising at least about360 grams per liter (on an acid equivalent basis) ofN-(phosphonomethyl)glycine predominantly in the form of a salt thereof.The process comprises hydrolyzing a dialkyl intermediate comprisingdialkyl N-(phosphonomethyl)glycine, a carboxylate salt of dialkylN-(phosphonomethyl)glycine or other ester intermediate produced byreaction of a dialkyl phosphite with N-methylolglycine, to yield asolution comprising glyphosate or an agronomically acceptable salt ofglyphosate; and recovering solid glyphosate acid or an aqueousconcentrate comprising an agronomically acceptable salt of glyphosate ina concentration of at least about 360 grams per liter a.e.

The present invention further provides a method of supplying aglyphosate product for applications in which it is desirable to maintainthe N-(phosphonomethyl)iminodiacetic acid content of the product atconsistently less than about 0.06 wt. % on a glyphosate basis. Themethod comprises producing glyphosate in a manufacturing facility, theproduction of glyphosate in such facility comprising catalytic oxidationof N-(phosphonomethyl)iminodiacetic acid in an aqueous medium in thepresence of a catalyst for the oxidation; during designated operationswithin the facility, conducting the process under conditions effectiveto consistently produce a glyphosate product having anN-(phosphonomethyl)iminodiacetic acid content less than about 0.06 wt.%, basis glyphosate; and segregating the glyphosate produced during thedesignated operations from other glyphosate product produced duringother operations wherein the other glyphosate product has anN-(phosphonomethyl)iminodiacetic acid content greater than about 0.06wt. %, basis glyphosate.

In a further aspect of the invention, a method for screening aherbicidal glyphosate formulation for use in foliar application to acrop of transgenic glyphosate-tolerant plants subject to leaf necrosiscaused by N-(phosphonomethyl)iminodiacetic acid or a salt thereofpresent in herbicidal glyphosate formulations is provided. The methodcomprises (a) growing a plant of the crop until a predetermineddevelopmental age or for a predetermined interval of time; (b) applyingthe herbicidal glyphosate formulation comprisingN-(phosphonomethyl)glycine or a salt thereof to the plant; (c)maintaining the treated plant for a predetermined interval of time underpredetermined temperature and humidity conditions selected to illicit aleaf necrosis injury response in the plant caused byN-(phosphonomethyl)iminodiacetic acid or a salt thereof present in theherbicidal glyphosate formulation; and (d) determining extent of leafnecrosis injury to the plant.

Further aspects and embodiments of the invention are described in thefollowing specification and detailed in the claims set forth below.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic flow sheet illustrating a continuous process forthe manufacture of glyphosate from N-(phosphonomethyl)iminodiaceticacid, in which the modifications of the present invention for productionof a low N-(phosphonomethyl)iminodiacetic acid content glyphosateproduct may be implemented;

FIG. 2 is a schematic flow sheet illustrating an alternative embodimentof the process of FIG. 1 in which N-(phosphonomethyl)iminodiacetic acidthat accumulates in the product recovery area can be removed from theprocess in a controlled manner, more particularly in a manner thatallocates N-(phosphonomethyl)iminodiacetic acid removal between a solidglyphosate acid product, a concentrated glyphosate salt solution, and apurge stream;

FIG. 3 is a schematic flow sheet illustrating an exemplary ion exchangesystem, which may be used in conjunction with the process for themanufacture of glyphosate illustrated in FIG. 1 or 2;

FIG. 4 is a schematic flow sheet illustrating an evaporativecrystallization system modified to accommodate lowN-(phosphonomethyl)iminodiacetic acid (PMIDA) content in the feedsolution without excessive fouling of the heat exchange surfaces andwhich may be used in conjunction with the process for the manufacture ofglyphosate illustrated in FIG. 1 or 2;

FIG. 5 is a graphical representation of the degree of necrosis reductionin ROUNDUP READY FLEX cotton 2 days after treatment (2 DAT) followingfield application of ROUNDUP WEATHERMAX-type glyphosate herbicidalformulations (0.4% PMIDA) safened with ferric sulfate addition inExample 2A.

FIG. 6 is a graphical representation of the degree of necrosis reductionin ROUNDUP READY FLEX cotton 2 days after treatment (2 DAT) followingfield application of ROUNDUP WEATHERMAX-type glyphosate herbicidalformulations with varying PMIDA levels and safened with fixed levels ofiron in Example 2B.

FIG. 7 is a graphical representation of the average necrosis anddistribution in ROUNDUP READY FLEX cotton 2 days after treatment (2 DAT)following field application of ROUNDUP ORIGINALMAX-type glyphosateherbicidal formulations (0.4% PMIDA) and varying ratios of iron to PMIDAin Example 2C.

FIG. 8 is a graphical representation of the degree of necrosis reductionin ROUNDUP READY FLEX cotton 2 days after treatment (2 DAT) followingfield application of ROUNDUP ORIGINALMAX-type glyphosate herbicidalformulations with varying PMIDA levels and safened with fixed levels ofiron in Example 2D.

FIG. 9 is a graphical representation of the average necrosis anddistribution in ROUNDUP READY FLEX cotton 2 days after treatment (2 DAT)following field application of: ROUNDUP WEATHERMAX or ROUNDUPORIGINALMAX-type glyphosate herbicidal formulations (0.4% PMIDA) andvarying ratios of iron to PMIDA; or ROUNDUP WEATHERMAX-type glyphosateherbicidal formulations of low PMIDA content (0.06% PMIDA) withoutferric sulfate addition in Example 2E.

FIG. 10 is the chromatogram (first isocratic solvent system) for aniron-containing glyphosate formulation concentrate subjected to thehigh-pressure liquid chromatography analytical procedure of Example 3 todetermine the concentration of PMIDA in the formulation concentrate; and

FIG. 11 is the chromatogram (alternative isocratic solvent system) foran iron-containing formulation concentrate subjected to thehigh-pressure liquid chromatography analytical procedure of Example 3 todetermine the concentration of PMIDA in the formulation concentrate.

DETAILED DESCRIPTION OF THE INVENTION

In accordance with the present invention, it has been discovered thatthe leaf necrosis phenomenon sometimes observed in transgenicglyphosate-tolerant cotton plants following over-the-top application ofglyphosate herbicides and under certain growing conditions is induced,at least in part, by N-(phosphonomethyl)iminodiacetic acid (PMIDA)and/or salts thereof which are often present at relatively lowconcentrations in glyphosate herbicidal formulations. One conventionalmethod of glyphosate manufacture, discussed in greater detail below,includes liquid phase catalytic oxidative cleavage of a carboxymethylsubstituent from PMIDA (formula (1)) to produceN-(phosphonomethyl)glycine (formula (2)) in accordance with thefollowing reaction:

Under commercial scale conditions, high conversion of the PMIDA to theN-(phosphonomethyl)glycine product is readily attained. However, lowconcentrations (e.g., from about 0.15% to about 0.6% by weight drybasis) of unreacted PMIDA typically remain in the manufactured technicalgrade N-(phosphonomethyl)glycine product isolated from the oxidationreaction mixture. Moreover, PMIDA may also be present as a by-product orcontaminant in N-(phosphonomethyl)glycine manufactured by otherconventional methods known in the art. Residual PMIDA in manufacturedN-(phosphonomethyl)glycine products is thus often present in herbicidalglyphosate compositions formulated using these products. Given therelatively limited water solubility of the organic acidN-(phosphonomethyl)glycine, aqueous herbicidal glyphosate compositionsare typically formulated using one or more of the more water-soluble andagronomically acceptable salts of glyphosate and, in such cases, thePMIDA is also predominantly present in the composition as thecorresponding salt, typically the corresponding mono- or di-basic salt.As used herein, unless the context requires otherwise, the term “PMIDA”includes N-(phosphonomethyl)iminodiacetic acid and/or salts and otherderivatives thereof and the term “glyphosate” includes any herbicidallyeffective form of N-(phosphonomethyl)glycine that results in theproduction of the glyphosate anion in plants, including glyphosate acidand/or salts or other derivatives thereof.

In most applications, the low levels of PMIDA typically present inglyphosate herbicidal formulations are not a problem. However, as notedabove, cotton, including transgenic glyphosate-tolerant cottonvarieties, is susceptible under certain growing conditions todevelopment of leaf necrosis induced by the presence of even relativelylow levels of PMIDA often found in commercial herbicidal glyphosateformulations. As susceptibility to PMIDA-induced necrosis is common toboth glyphosate-tolerant cotton (i.e., transgenic cotton) as well asnon-transgenic cotton, it appears that the PMIDA-induced leaf necrosisphenomenon in glyphosate-tolerant cotton is unrelated to the transgene.PMIDA-induced leaf necrosis sometimes observed in transgenicglyphosate-tolerant cotton such as ROUNDUP READY and ROUNDUP READY FLEXcotton varieties is characterized by a rapid onset of symptomology,typically within about 2 days following over-the-top application ofglyphosate herbicides. Additional symptom development beyond this periodfor the most part has not been observed, indicating that this phenomenonis not a systemic effect. Furthermore, symptom expression appears to belight activated.

Without being bound to any particular theory, these observations suggestthat PMIDA-induced necrosis may operate through a mechanism similar tothat seen with herbicides that function through the inhibition of theprotoporphyrinogen-oxidase (PPO) enzyme. PPO is inhibited by a widerange of herbicides, such as, the diphenylethers, oxadiazoles, cyclicimides, phenyl pyrazoles and pyridine derivatives. PMIDA could actthrough the same mechanism as those herbicides wherein membranedisruption is initiated by the inhibition of PPO in the last stages ofchlorophyll and heme biosynthetic pathways leading to a buildup ofphytotoxic intermediates such as free radicals resulting in tissuenecrosis. More particularly, it is believed that PPO catalyzes theoxidation of protoporphyrinogen IX (PPGIX) to protoporphyrin IX (PPIX).PPO inhibition leads to an accumulation of PPGIX, the firstlight-absorbing chlorophyll precursor. PPGIX accumulation is apparentlytransitory as it overflows its normal environment in the thylakoidmembrane and oxidizes to PPIX. This oxidation may be catalyzed by aplasmalemma enzyme that has protox activity, but is insensitive to, itis believed, PMIDA. PPIX formed outside its native environment probablyis separated from Mg chelatase and other pathway enzymes that normallyprevent accumulation of PPIX. Light absorption by PPIX apparentlyproduces triplet state PPIX which interacts with ground state oxygen toform singlet oxygen. Both triplet PPIX and singlet oxygen can abstract ahydrogen from unsaturated lipids, producing a lipid radical andinitiating a chain reaction of lipid peroxidation. Lipids and proteinsare attacked and oxidized, resulting in loss of chlorophyll andcarotenoids and in leaky membranes which allows cells and cellorganelles to dry and disintegrate rapidly. Quoting from HerbicideHandbook (William K. Vencill ed., Weed Science Society of America, 8thedition, pages 69 and 329-330, (2002)).

The expression of PMIDA-induced leaf necrosis and the severity of theresulting leaf injury are heavily dependent upon the prevailing growingconditions and environmental factors and is generally more severe as thePMIDA concentration in the glyphosate herbicidal composition andapplication rate increase. More particularly, conditions that favor slowmetabolism in the cotton plant or metabolic stress generally followingglyphosate application appear to be a key factor contributing to theonset and severity of leaf necrosis. For example, it has been observedthat exposure to low temperatures is a contributor to PMIDA-induced leafdamage observed in greenhouse and growth chamber environments. It hasbeen found that glyphosate-tolerant cotton plants experiencing “cool”growing conditions (i.e., maximum temperatures of about 80° F. (27° C.)or less) following foliar application of glyphosate herbicides havesignificantly increased tendency to exhibit leaf injury as compared toplants experiencing “hot” growing conditions (i.e., maximum temperaturesof about 90° F. (32° C.). Cotton plants experiencing maximumtemperatures of about 70° F. (21° C.) following glyphosate applicationshowed a similar amount of leaf damage as compared to plants grown at80° F. It has been further observed that cool growing conditionsfollowing glyphosate application produced significantly greater leafinjury than cool growing conditions experienced prior to glyphosatetreatment. It is believed that cotton plant metabolism at growingtemperatures of at least about 90° F. is sufficient to overcome theeffects of PMIDA levels typically present in the glyphosate composition,but at 80° F. and lower maximum growing temperatures, plant metabolismmay be too slow to overcome these effects, with resultant leaf damage.

If PMIDA-induced necrosis is observed, injury can range from minornecrotic lesions affecting on average from about 1% to about 5% of thetotal leaf surface area of the plant to more pronounced necrotic lesionsaffecting on average about 5%, 10%, 15%, 20%, 25%, 30% or more of thetotal leaf surface area of the affected plants. Minor necrotic lesionsgenerally appear as multiple, very small, circular shaped and uniformlydistributed lesions on the surface of the treated cotton leaf having adiameter of less than about 0.5 cm and may coalesce into larger necroticlesions in the form of larger circular or irregularly shaped areas orpatches on the treated cotton leaf surface having a largest dimension ofgreater than about 0.5 cm. In severe cases, necrotic lesions can becomesufficiently large to result in highly visible leaf damage, or even lossof the affected leaves. PMIDA-induced leaf necrosis or tissue death isvisibly distinct from “surfactant burn” such as “window panes” commonlyassociated with the use of certain surfactants in herbicidalformulations applied to glyphosate-tolerant crops.

In accordance with the present invention, a variety of strategies havebeen devised to allow for effective weed control in cotton productionfrom transgenic glyphosate-tolerant cotton plants using glyphosateherbicidal compositions while mitigating PMIDA-induced necrosis so as toavoid significant leaf damage to the cotton crop grown under variableenvironmental conditions. One general approach is to control or limitthe concentration of PMIDA in the manufactured glyphosate product and inturn the herbicidal glyphosate composition formulated using the productso that at the requisite application rate necessary to attain adequateweed control in the cotton crop, significant leaf necrosis is notinduced in the treated plants. However, in some circumstances, a sourceof manufactured glyphosate having a sufficiently low concentration ofPMIDA may be unavailable or it may be cost prohibitive or otherwiseimpractical to obtain or produce such a glyphosate product. Accordingly,another aspect of the present invention is to include in the glyphosateherbicidal composition containing appreciable levels of PMIDA certainsafening agents that act to mitigate or inhibit PMIDA-induced necrosisin the cotton crop.

Although susceptibility to PMIDA-induced necrosis is common to cottongenerally, this potential for leaf damage is particularly problematic intransgenic glyphosate-tolerant cotton plants because these varieties areengineered to allow over-the-top application of glyphosate herbicides.Accordingly, the strategies and methods disclosed herein for mitigatingPMIDA-induced necrosis are particularly intended for the control ofweeds in cotton production from transgenic glyphosate-tolerant cottonplants.

As used herein transgenic glyphosate-tolerant cotton plants includesplants grown from the seed of any cotton event that provides glyphosatetolerance and glyphosate-tolerant progeny thereof. Suchglyphosate-tolerant cotton events include, without limitation, thosethat confer glyphosate tolerance by the insertion or introduction, intothe genome of the plant, the capacity to express various native andvariant plant or bacterial EPSPS enzymes by any genetic engineeringmeans known in the art for introducing transforming DNA segments intoplants to confer glyphosate resistance as well as glyphosate-tolerantcotton events that confer glyphosate tolerance by other means such asdescribed in U.S. Pat. Nos. 5,463,175 and 6,448,476 and InternationalPublication Nos. WO 2002/36782, WO 2003/092360 and WO 2005/012515.

Non-limiting examples of transgenic glyphosate-tolerant cotton eventsinclude the current commercial ROUNDUP READY cotton event designated1445 and described in U.S. Pat. No. 6,740,488. Of particular interest inthe practice of the present invention are methods for weed control in acrop of transgenic glyphosate-tolerant cotton plants in which glyphosateresistance is conferred in a manner that allows later stage applicationof glyphosate herbicides without incurring significantglyphosate-mediated reproductive injury. Non-limiting examples of suchtransgenic glyphosate-tolerant cotton plants include those grown fromthe seed of the ROUNDUP READY FLEX cotton event (designated MON 88913and having representative seed deposited with American Type CultureCollection (ATCC) with Accession No. PTA-4854) and similarglyphosate-tolerant cotton events and progeny thereof as described inInternational Publication No. WO 2004/072235. ROUNDUP READY FLEX cottonevent MON 88913 and similar glyphosate-tolerant cotton events may becharacterized in that the genome comprises one or more DNA moleculesselected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ IDNO:3, and SEQ ID NO:4; or the genome in a DNA amplification methodproduces an amplicon comprising SEQ ID NO:1 or SEQ ID NO:2; or thetransgenic glyphosate-tolerant cotton plants comprise a glyphosatetolerant trait that is genetically linked to a complement of a markerpolynucleic acid, and the marker polynucleic acid molecule is homologousor complementary to a DNA molecule selected from the group consisting ofSEQ ID NO:1 and SEQ ID NO:2 as described in International PublicationNo. WO 2004/072235, the entire contents of which are incorporated hereinby reference. A sequence listing containing each of SEQ ID NOS: 1, 2, 3,and 4 as disclosed in International Publication No. WO 2004/072235 iscontained herein. These sequences are listed as SEQ ID NOS: 1, 2, 3, and4, respectively.

As noted above, the ROUNDUP READY FLEX cotton event MON 88913 allows forover-the-top application of glyphosate herbicides at advanced stages ofplant development without incurring significant glyphosate-mediatedreproductive injury (e.g., as quantified, for example, by flower pollenshed and/or lint yield). As compared to the previous commercial ROUNDUPREADY cotton event designated 1445, ROUNDUP READY FLEX cotton event MON88913 is particularly advantageous in allowing foliar application ofglyphosate herbicide for weed control at a developmental agecharacterized by at least five leaf nodes present on a cotton plant ofthe crop. As used herein, a node having a leaf branch is referred to asa leaf node in accordance with the conventional node method used inassessing cotton plant developmental age. Furthermore, cotyledons areleaves originally contained in the seed and are not considered as plantleaves or nodes for purposes of determination of the stage of cottondevelopment. That is, as generally accepted by those skilled in the artand as used herein, the stem point of cotyledon attachment is referencedas Node 0. The fifth and subsequent leaf nodes are typically the firstreproductive (i.e., fruiting) branches and may develop a fruiting budand associated leaf. A leaf node having a reproductive branch may bereferred as a reproductive node. Cotton plants can develop as many asabout 25 leaf nodes, with nodes 5-25 potentially developing intoreproductive nodes. In practicing weed control in a crop of transgenicglyphosate-tolerant cotton grown from seed of ROUNDUP READY FLEX cottonevent MON 88913 or similar cotton events and progeny thereof, glyphosateherbicidal formulations can be applied over-the-top of the crop at moreadvanced developmental ages characterized, for example, by six, ten,twelve, fourteen or more leaf nodes present on a cotton plant of thecrop and up to and including layby without incurring significantglyphosate-mediated reproductive injury to the crop. The herbicidalglyphosate formulation may be applied over-the-top of the cotton crop atvarious intervals of advanced development, characterized, for example,by six or more leaf nodes and no more than ten, twelve, fourteen,sixteen, eighteen, twenty or twenty-five leaf nodes on a cotton plant ofthe crop. The strategies and methods disclosed herein for mitigatingPMIDA-induced necrosis are particularly advantageous in weed controlmethods used in cultivation of ROUNDUP READY FLEX cotton and similarevents that permit such later stage over-the-top application ofglyphosate herbicides since the appearance of necrotic lesions on thetreated cotton plants may appear to be more pronounced due to the morefully developed canopy and greater available leaf area.

By employing the various strategies discussed in detail below,PMIDA-induced leaf necrosis in transgenic glyphosate-tolerant cotton canbe substantially avoided under the relevant growing conditions or atleast sufficiently mediated or inhibited. The extent of leaf necrosis isreadily quantified by plant biologists and technicians through visualassessment of the area of any necrotic lesions relative to the totalleaf surface area of the cotton plants following treatment with aglyphosate herbicide. In the practice of the weed control methods of thepresent invention, PMIDA-induced necrotic lesions on the surface of theleaves of the transgenic glyphosate-tolerant cotton plants are generallyinhibited so as on average to account for no more than about 25% of thetotal leaf area of the plants of the treated crop. Preferably, necroticlesions on the surface of the leaves of the cotton plants treated inaccordance with the present invention on average account for no morethan about 20%, and even more preferably no more than about 15% of thetotal leaf area of the plants of the treated crop. By practicing themore preferred embodiments of the present invention disclosed herein,PMIDA-induced necrotic lesions on the surface of the leaves of thecotton plants may be advantageously inhibited so as to on averageaccount for no more than about 10% or no more than about 5% of the totalleaf area of the plants of the treated crop. In accordance withespecially preferred embodiments of the present invention, onset ofPMIDA-induced necrosis is substantially avoided under all relevantgrowing conditions including those noted above and discussed below thatmight otherwise tend to enhance the onset and severity of PMIDA-inducednecrosis.

As noted above, the onset and severity of PMIDA-induced leaf necrosis intransgenic glyphosate-tolerant cotton plants is dependent on theprevailing growing conditions as well as the concentration of PMIDA inthe glyphosate herbicide applied to the plants. In accordance with thepresent invention, it has been determined that under many growingconditions and at typical glyphosate application rates necessary foradequate weed control (e.g., at rates of from about 0.75 to about 1.125lb glyphosate a.e./A or about 0.84 to about 1.26 kg glyphosate a.e./ha)significant PMIDA-induced leaf necrosis can generally be avoided bycontrolling the concentration of PMIDA in the herbicidal glyphosatecomposition such that the application rate of PMIDA is no more thanabout 2.5 g PMIDA acid equivalent per hectare, preferably no more thanabout 2.2 g PMIDA acid equivalent per hectare, more preferably no morethan about 2 g PMIDA acid equivalent per hectare, and even morepreferably no more than about 1.7 g PMIDA acid equivalent per hectare.However, because cotton plant susceptibility to PMIDA-induced necrosisis dependent upon environmental conditions that may vary widely from onegrowing location to another and throughout the growing season, in orderto provide a safety factor and more consistently avoid the risk ofexpression of leaf injury, it is preferred to control the concentrationof PMIDA in the herbicidal glyphosate composition and the applicationrate of the composition to the cotton plants to further reduce theapplication rate of PMIDA to no more than about 1.5 g PMIDA acidequivalent per hectare, even more preferably no more than about 1.2 gPMIDA acid equivalent per hectare, and still more preferably no morethan about 1 g PMIDA acid equivalent per hectare. In accordance witheven more preferred embodiments of the present invention, theconcentration of PMIDA in the herbicidal glyphosate composition and theapplication rate of the composition are controlled such that theapplication rate of PMIDA is no more than about 0.7 g PMIDA acidequivalent per hectare, even more preferably no more than about 0.5 gPMIDA acid equivalent per hectare and especially no more than about 0.25g PMIDA acid equivalent per hectare.

As apparent to those skilled in the art, based on typical glyphosateapplication rates necessary for adequate weed control in transgenicglyphosate-tolerant cotton (e.g., at rates of from about 0.75 to about1.125 lb glyphosate a.e./A or about 0.84 to about 1.26 kg glyphosatea.e./ha), the composition including the concentration of PMIDA in theherbicidal glyphosate formulation applied to the plants, concentratesfrom which such formulations are prepared and ultimately the compositionof the manufactured technical grade glyphosate product from which suchcompositions are prepared can be readily determined. Glyphosatemanufacturing processes such as those including the oxidative cleavageof a PMIDA substrate or those utilizing glycine can be readily practicedor modified to produce a technical grade N-(phosphonomethyl)glycineproduct of sufficient glyphosate assay and having a PMIDA concentrationsuitable for producing herbicidal glyphosate compositions capable ofachieving PMIDA application rates so as to not induce significant leafnecrosis in the treated plants. Exemplary process strategies forproducing manufactured technical grade glyphosate products havingsufficiently low PMIDA content are described in detail below.

In some situations, a source of manufactured glyphosate having asufficiently low concentration of PMIDA may be unavailable or it may becost prohibitive or otherwise impractical to obtain or produce such aglyphosate product. That is, it may not always be feasible oreconomically practical to control the concentration of PMIDA in theherbicidal glyphosate composition applied to the cotton plants at therate necessary to attain adequate weed control while minimizing thePMIDA application rate to an extent sufficient to avoid inducingsignificant leaf necrosis in the treated plants. However, in accordancewith another aspect of the present invention, glyphosate herbicidalcomposition containing appreciable levels of PMIDA (e.g., correspondingto an application rate in excess of about 2.5 g PMIDA acid equivalentper hectare and up to about 5 g or 10 g PMIDA acid equivalent perhectare or higher) that might otherwise lead to leaf necrosis can besafened by the inclusion of certain PMIDA safening agents or safenersthat act to mitigate or inhibit PMIDA-induced necrosis in the cottoncrop. Furthermore, even glyphosate herbicidal formulations containingreduced levels of PMIDA sufficient to attain a PMIDA application rate ofno more than about 2.5 g PMIDA acid equivalent per hectare may furtherinclude a safening agent as an added measure of protection againstPMIDA-induced necrosis.

Several classes of PMIDA safening agents suitable for inclusion inglyphosate herbicidal compositions containing PMIDA have beendiscovered. Some of these safening agents are believed to inhibitsignificant PMIDA-induced leaf necrosis by inhibiting buildup ofphytotoxic free radicals in the tissues of cotton plants that mightotherwise lead to membrane disruption and tissue death. Non-limitingexamples of safening agents that interrupt free radical formationresulting from uptake of PMIDA in the foliar tissues of the treatedcotton plants include antioxidants, certain metal ions and lightabsorbing compounds.

Antioxidants are believed to mitigate PMIDA-induced leaf necrosis byscavenging and destroying free radicals generated in the treated cottonplants. Indeed, observed reduction of PMIDA-induced necrosis through theuse of antioxidants in accordance with the present invention is furtherevidence that the necrosis phenomenon is at least in part the result offree radical formation. More particularly, antioxidants added toglyphosate formulations of the present invention are believed toscavenge free radicals and retard the oxidation of organic plantmaterials such as lipids and proteins that can result in plant tissuedamage such as by loss of chlorophyll and carotenoids and in leaky cellmembranes with concomitant cell and cell organelle drying anddisintegration.

Suitable antioxidants or free radical scavengers include thoseconsidered as generally recognized as safe (GRAS) as specified in 21C.F.R. §182. For example, safening antioxidants may be selected fromascorbic acid, dehydroascorbic acid, ascorbyl palmitate, ascorbylstearate, sodium ascorbate, sorbic acid, sodium sorbate, potassiumsorbate, anoxomer, retinol, resorcinol, the various tocopherols andtocophatrienes (e.g., D-α-tocopheryl acetate, D-α-tocopheryl acidsuccinate, D-β-tocopherol, D-γ-tocopherol, D-δ-tocopherol,D-α-tocotrienol, D-β-tocotrienol, Dγ-tocotrienol, DLα-tocopherol,DL-α-tocopheryl acetate, DL-α-tocbpheryl calcium succinate,DL-α-tocopheryl nicotinate, DL-α-tocopheryl linoleate/oleate andderivatives or stereo isomeric forms thereof), hydroquinone, butylatedhydroxytoluene (BHT), butylated hydroxyanisole (BHA), t-butylhydroquinone (TBHQ), propyl gallate, dodecyl gallate, isoamyl gallate,octyl gallate, reduced coenzyme-Q, flavones and isoflavones such asapigenin, quercetin, genistein and daidzein, pycnogenol, ubiquinone,ubiquinol, monosodium glutamate, butylated hydroxymethylphenol, dilaurylthiodipropionate, disodium ethylenediamine tetraacetate, tartaric acid,erythorbic acid, sodium erythorbate, ethoxyquin, ethyl protocatechuate,guaiac resin, gum guaiac, isopropyl citrate, monoglyceride citrate,lecithin, nordihydroguaiaretic acid, phosphoric acid, potassium lactate,potassium metabisulfite, potassium sulfite, sodium hypophosphite, sodiumlactate, sodium metabisulfite, sodium sulfite, sodium thiosulfate,stannous chloride, tertiary butylhydroquinone,3-t-butyl-4-hydroxyanisole, calcium ascorbate, calcium disodium EDTA,catalase, cetyl gallate, clove extract, coffee bean extract,2,6-di-t-butylphenol, disodium citrate, edetic acid,6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline, ethyl gallate, ethylmaltol, eucalyptus extract, fumaric acid, gentian extract, glucoseoxidase, heptyl paraben, hesperetin,4-hydroxymethyl-2,6-di-t-butylphenol, N-hydroxysuccinic acid, lemonjuice, lemon juice solids, maltol, methyl gallate, methylparaben,phosphatidylcholine, pimento extract, potassium bisulfite, potassiumsodium tartrate anhydrous, rice bran extract, rosemary extract, sageextract, sodium ascorbate, sodium erythorbate, sodium hypophosphate,sodium hypophosphate, sodium thiosulfate pentahydrate, soy flour,sucrose, α-terpineol, tocopherol, D-α-tocopherol, DL-α-tocopherol,tocopheryl acetate, D-α-tocopheryl acetate, DL-α-tocopheryl acetate,2,4,5-trihydroxybutyrophenone, wheat germ oil, thiodipropionic acid andmixtures thereof. In some cases, a combination of antioxidants is usedas the safening agent wherein the antioxidants work together to producean effect in mitigating PMIDA-induced necrosis that is greater than thatachieved using a comparable amount of each antioxidant individually.

Experimental results indicate that all antioxidants evaluated showedsome ability to counteract PMIDA-induced necrosis in glyphosate treatedcotton. In accordance with a preferred embodiment, the antioxidantsafening agent is selected from hydroquinone, resorcinol, BHA, BHT andmixtures thereof.

The requisite amount of antioxidant to add to the herbicidal glyphosatecompositions to avoid significant PMIDA-induced necrosis in the treatedcotton plants depends on the PMIDA concentration, the selectedantioxidant or combination of antioxidants and the relative ability ofthe antioxidant safening agent to scavenge free radicals and may bereadily determined empirically by one skilled in the art through routineexperimentation. The safening agent comprising one or more antioxidantsis preferably added to herbicidal glyphosate compositions, includingconcentrates and tank mixes, at a molar ratio to PMIDA of from about50:1 to about 1:1, from about 40:1 to about 1:1, from about 30:1 toabout 1:1, from about 20:1 to about 1:1, from about 15:1 to about 1:1,from about 10:1 to about 1:1, from about 5:1 to about 1:1, from about3:1 to about 1:1, or even from about 2:1 to about 1:1.

Certain metal ions present in the herbicidal glyphosate compositions mayalso act as a safening agent to mitigate PMIDA-induced leaf necrosis inthe treated cotton plants. PMIDA, by virtue of the presence of carboxyland a phosphonomethyl groups or ligands, can function as a strongcomplexing agent and can chelate or otherwise bind with free metal ionsin solution and thereby be sequestered (e.g., not taken up into thefoliar tissues of the cotton plant) or otherwise rendered bio-inactiveto the cotton plant. PMIDA present in glyphosate compositions isbelieved to selectively bind or otherwise form a complex (e.g., a (II)or (III) coordination complex or chelate) or salt with metal ions andthereby render it biologically unavailable in the formation of freeradicals in the cotton plant. That is, the metal ion added to thecomposition is subject to formation of a complex or salt with PMIDA(e.g., N-(phosphonomethyl)iminodiacetic acid or an anion formed bydeprotonation or partial deprotonation thereof). Importantly, PMIDAforms more stable complexes with such metal ions than does glyphosatesuch that the PMIDA and not the glyphosate selectively complexes orbinds with the metal ions, thereby avoiding significant negative impacton herbicidal activity that would occur if a significant amount ofglyphosate were rendered inactive by complexing or binding with themetal ion.

The metal ion added to the glyphosate composition as a PMIDA safeningagent may be any transition metal or other metal and is preferablyagronomically acceptable and recognized as inert for permitted use inagricultural herbicide compositions. Suitable non-limiting examples ofmetal ion safening agents include aluminum, antimony, iron, chromium,nickel, manganese, cobalt, copper, zinc, vanadium, titanium, molybdenum,tin, barium and mixtures thereof. In one preferred embodiment, the metalion is selected from aluminum, copper, iron, zinc and mixtures thereof.In another preferred embodiment, the safening agent comprises iron ionsor a mixture of iron ions and zinc ions or a mixture of iron ions andcopper ions. In one preferred embodiment, the metal ion safening agentadded to the herbicidal composition for selective complexing or bindingwith PMIDA comprises a polyvalent metal ion (e.g., Fe(III), Al(III),Zn(II), and Cu(II)).

The metal ion introduced into herbicidal glyphosate compositions may bederived from various salts (e.g., the salt of a strong acid such as ametal chloride or metal sulfate or the salt of a di-, tri- or otherpolycarboxylic acid or derivative) or other compounds by dissociation ordissolution in the composition or from the elemental metal. Suitablesource compounds for the metal ions include, without limitation,aluminum chloride, aluminum hydroxide, aluminum oxide, aluminum sulfate,antimony trioxide, barium carbonate, barium sulfate, cobalt carbonate,cobalt sulfate, copper acetate, copper carbonate, copper hydroxide,copper nitrate, copper sulfate, cupric oxide, cuprous oxide, ferricammonium sulfate, ferric chloride, ferric oxide, ferric oxide hydrate,ferric sulfate, ferrous ammonium sulfate, ferrous oxide, ferroussulfate, iron, iron salts of di-, tri- or other polycarboxylic acidssuch as iron citrate, iron hydroxide oxide, ferosoferric oxide, nickelchloride, nickel acetate, nickel sulfate, potassium aluminum sulfate,potassium permanganate, sodium aluminate, sodium aluminum phosphate,sodium chromate, sodium iron(III) ethylenediaminetetraacetate, sodiummolybdate, sodium permanganate, sodium potassium aluminum silicate, tinoxide, titanium sulfate, vanadyl sulfate, zinc acetate, zinc chloride,zinc hydroxide, zinc iron oxide, zinc naphthenate, zinc oxide, zincoxide sulfate (Zn₄O₃(SO₄)), zinc sulfate (basic), zinc sulfate(monohydrate) and mixtures thereof.

In one preferred embodiment, the metal ion safening agent added to theherbicidal composition for selective complexing or binding with PMIDAcomprises polyvalent iron (e.g., Fe(III)) and is derived from ferricammonium sulfate, ferric chloride, ferric oxide, ferric oxide hydrate,ferric sulfate, ferrous ammonium sulfate, ferrous oxide, ferrous sulfateand/or iron salts of di-, tri- or other polycarboxylic acids such asiron citrate. In one preferred embodiment, a safening agent comprisingpolyvalent iron ions in the herbicidal glyphosate composition is derivedfrom ferric sulfate, ferric chloride and/or iron citrate.

When preparing glyphosate concentrate compositions containing certainmetal ion safening agents such as iron derived from iron oxide, ferricchloride or ferric sulfate, it may be necessary to first mix the metalion with a suitable solubilizing or stabilizing ligand (sL) in anaqueous solution before combining it with the PMIDA-containingglyphosate. For example, aqueous solutions of the metal ion andsolubilizing ligand may be mixed and then the mixture combined withglyphosate and other components of the composition. This practiceinhibits precipitation of a metal salt of glyphosate and/or theprecipitation of metal hydroxide in the composition thereby renderingthe metal ion unavailable for complexing or binding with PMIDA. Theseverity of these solubility issues appears to be somewhat dependentupon the identity of the metal salt of glyphosate included in theconcentrate composition and, for example, is more problematic whenpreparing iron safened concentrate compositions containing the potassiumsalt of glyphosate as compared to the isopropylamine salt of glyphosate.The solubilizing or stabilizing ligand, is selected to (1) form acomplex with the metal ion with sufficient stability to be competitivewith glyphosate's metal complex stability and sufficiently stable toprevent any metal salt hydrolysis to metal hydroxides at the pH of thecomposition (typically pH of 4 to 5); and (2) form a complex weaker thanthat formed by PMIDA, thereby allowing PMIDA to displace and replacethis solubilizing ligand from the metal in the final composition. Themetal-ligand formation constants are used to quantify the complex'sstability, and can be readily determined by potentiometric titration orfound in the literature. The complex stability for the solubilizingligand can also be controlled by adjusting the amount used relative tothe metal ion. Specifically, the molar ratio of solubilizing ligand tometal ion is optimized to eliminate the adverse effects that areobserved on herbicidal activity and formulation homogeneity, detailedabove, when simple, aqueous metal ions are used. This molar ratio istypically greater than 1, and is usually from about 1.5 to about 4(sL/metal). The composition will thus contain three primary materialscapable of complexing or binding with the metal ion (i.e., in order ofdecreasing stability, decreasing metal-ligand formation constantPMIDA>sL˜ glyphosate). Examples of suitable solubilizing ligands includepolyacids (e.g., polycarboxylic acids) and hydroxyl acids like citricacid, gluconic acid, oxalic acid, malonic acid, succinic acid, malicacid, tartaric acid, fumaric acid, maleic acid, glutaric acid,dimethylglutaric acid, adipic acid, trimethyladipic acid, pimelic acid,tartronic acid, suberic acid, azelaic acid, sebacic acid,1,12-dodecanedioic acid, 1,13-tridecanedioic acid, glutamic acid,phthalic acid, isophthalic acid, lactic acid, terephthalic acid, or ananhydride, ester, amide, halide, salt or precursor of any of theseacids, polyhydroxy compounds like fructose and catechol, amino acids,proteins and polysaccharides. In accordance with one preferredembodiment, the solubilizing ligand comprises a polycarboxylic acid suchas citric acid.

An additional complication exists with aqueous solutions of iron (III).At a pH of up to about 2, ferric iron has a strong tendency to hydrolyzeto form a binuclear species, [Fe(H₂O)4(OH)2Fe(H₂O)4]⁴⁺ and at a pH aboveabout 2 to 3 polynuclear Fe—OH species. The latter results in theprecipitation of colloidal or hydrous ferric oxide. Glyphosatecompositions have a pH around 4.5 units. However, this problem canlikewise be overcome by employing a suitable solubilizing ligand asdescribed above. The solubilizing ligand selected (e.g., citric acid,fructose) possesses a metal stability constants less than that of PMIDA,to allow PMIDA to displace the solubilizing ligand, but stable enough toprevent hydrolysis of Fe(III) as described above. As an alternative toor in addition to using a solubilizing ligand to overcome solubility andprecipitation issues that might arise when preparing glyphosateconcentrate compositions containing certain metal ion safening agents,it may be advantageous to use a mixture of metal ions to prepare asuitable safened concentrate. For example, a combination of iron ionsand zinc ions or a combination of iron ions and copper ions may beemployed.

The amount of metal ion safening agent introduced into the compositionrelative to PMIDA is selected to ensure the reduction of free (i.e.,non-bound or non-complexed) PMIDA to a level sufficiently low so as tonot induce significant leaf necrosis in the cotton crop and can bereadily determined through routine experimentation. The minimallyeffective molar ratio of metal ion safening agent to PMIDA in theherbicidal glyphosate composition depends upon the PMIDA concentration.As the concentration of PMIDA in the manufactured glyphosate productfrom which herbicidal glyphosate compositions such as concentrates andtank mixes are prepared decreases, a lower molar ratio of metal ionsafening agent to PMIDA (e.g., even less than 1:1) may be effectivelyutilized in the composition and satisfactory results obtained sincefree, biologically active PMIDA in the composition may be reduced by thesafening agent to a level that prevents significant PMIDA-inducednecrosis in the treated cotton plants at the designated applicationrate. The safening agent comprising one or more metal ions is generallyadded to herbicidal glyphosate compositions, including concentrates andtank mixes, at a molar ratio to PMIDA of at least about 0.15:1, at leastabout 0.2:1, at least about 0.25:1, at least about 0.3:1, at least about0.35:1, at least about 0.4:1 and preferably at a molar ratio to PMIDA ofat least about 0.45:1, at least about 0.5:1, at least about 0.55:1, atleast about 0.6:1, at least about 0.65:1, at least about 0.7:1, at leastabout 0.75:1, at least about 0.8:1, at least about 0.85:1, at leastabout 0.9:1 or even at least about 0.95:1. Typically, the molar ratio ofthe metal ion safening agent to PMIDA in the herbicidal glyphosatecomposition is no greater than about 25:1, no greater than about 20:1,no greater than about 15:1, no greater than about 10:1, no greater thanabout 5:1, no greater than about 4:1, no greater than about 3:1 andpreferably no greater than about 2.5:1. Often the concentration of PMIDAin the manufactured glyphosate product is sufficiently high such thatthe molar ratio of the metal ion safening agent to PMIDA in theherbicidal glyphosate composition including concentrates and tank mixesis at least about 0.5:1, typically from about 0.5:1 to about 25:1, fromabout 0.5:1 to about 20:1, from about 1:1 to about 25:1, from about 1:1to about 20:1, from about 1:1 to about 15:1, from about 1:1 to about10:1, from about 1:1 to about 9:1, from about 1:1 to about 8:1, fromabout 1:1 to about 7:1, from about 1:1 to about 6:1, from about 1:1 toabout 5:1, from about 1:1 to about 4:1, preferably from about 1:1 toabout 3:1, more preferably from about 1:1 to about 2.5:1, and even morepreferably from about 1:1 to about 2:1. Utilizing a metal ion safeningagent in the glyphosate herbicidal compositions of the present inventionallows the application rate of free, biologically active PMIDA to bereduced to no more than about 2.5 g PMIDA acid equivalent per hectareand lower (e.g., as noted above and preferably no more than about 1.5 g,more preferably no more than about 1.2 g, more preferably no more thanabout 1 g, even more preferably no more than about 0.7 g, still morepreferably no more than about 0.5 g and especially no more than about0.25 g PMIDA acid equivalent per hectare) and thereby inhibitsignificant PMIDA-induced necrosis in the treated cotton plants.

In practicing the various embodiments of the present invention, it maybe necessary to determine the PMIDA content of a material such asmanufactured glyphosate product used in formulation of concentrates,tank mixes or other forms of herbicidal compositions or the PMIDAcontent of the formulated herbicidal compositions themselves, forexample, to determine whether a safening agent is necessary, thequantity of safening agent to be employed as well as to assurecompliance with the established compositional specifications. Analyticalmethods for determining PMIDA content are available to those skilled inthe art. One such method using a high-pressure liquid chromatographyprocedure (HPLC) is described in Example 3 below.

Similarly, in practicing the embodiment described herein calling for useof certain metal ion safening agents, it may be necessary to accuratelydetermine the metal ion content of an herbicidal glyphosate composition.Methods for analyzing a product or material to determine theconcentration of metal ions such as those disclosed herein suitable foruse as a safening agent are likewise available to those skilled in theart. By way of example, trace concentrations of iron in materials usedand produced in the practice of the present invention may be measuredusing the test method based on photometric determination of the1,10-phenanthroline complex formed with the iron(II) ion described inASTM E 394-94.

In accordance with another embodiment of the invention, the safeningagent included in the herbicidal glyphosate composition comprises alight absorbing compound that acts to protect the treated cotton plantfrom particular light spectra to inhibit free radical productionassociated with photo-activated PMIDA-induced necrosis. Generally, thelight absorbing compound is selected so as to preferentially block atleast a portion of the visible light spectrum near the wavelength(s)associated with PMIDA-induced free radical production in the treatedcotton plant and to transmit other portions of the visible lightspectrum necessary for adequate photosynthesis and plant health.

Suitable light absorbing compounds include certain dyes such as FD&Cyellow dye #5 (commonly known as tartrazine and having the chemical name3-carboxy-5-hydroxy-1-p-sulfophenyl-4-p-sulfophenylazopyrazole trisodiumsalt), FD&C Blue #1, FD&C Red #40, FD&C Red #33, FD&C Violet #1, FastGreen FCF, methylene blue and mixtures thereof. Tartrazine having amaximum light absorbance at a wavelength of about 425 nm, was tested asa safening agent in glyphosate spray solutions and found tosignificantly decrease PMIDA-induced necrosis in the treated cottonplants. The amount of tartrazine or other light absorbing compoundintroduced into the composition as a safening agent is selected toensure absorbance of at least a portion of the visible light spectrumnear the wavelength(s) associated with PMIDA-induced free radicalproduction in the treated cotton plant so as to reduce the formation offree radicals to a level sufficient to not induce significant leafnecrosis in the cotton crop and can be readily determined throughroutine experimentation. For example, the safening agent comprisingtartrazine or other dye is generally added to herbicidal glyphosatecompositions, including concentrates and tank mixes, in an amountsufficient such that at least about 50, 60, 70, 80 or 90% or more of theincident light at the relevant wavelength(s) is absorbed. The preferredamount depends on the identity of the dye or other light absorbingcompound and the relative ability of the material to absorb incidentlight at the relevant wavelength(s) associated with PMIDA-induced freeradical production. Some dyes and other light absorbing compounds have atendency to degrade or fade over time or upon exposure to light.Accordingly, in practicing this embodiment of the invention, it may beuseful to incorporate the dye or other light absorbing compound into theglyphosate composition just prior to use or to take other measures toensure the safening activity of the dye is not significantly diminished.

Humectants are another class of safening agents that may be employed inthe practice of the present invention to inhibit PMIDA-induced necrosisin treated cotton plants. Humectants are believed to mitigatePMIDA-induced necrosis by protecting or aiding in the repair of cellmembranes in the foliar tissues of the cotton plants damaged by freeradicals and/or by modifying or altering the leaf surface/herbicidalformulation interface, thus affecting the uptake of PMIDA. Without beingbound by any particular theory, it is postulated that humectants can beentrapped in the interstices of the cell wall surfaces, where they actas a hygroscopic agent, thus increasing the amount of water held in thisarea. The humectants employed in the compositions of this invention arepreferably water-soluble and are substantially non-ionizable. Bysubstantially non-ionizable it is meant that no significant ordetectable disassociation in water occurs. Such humectants can beemployed in addition to or substituted partially for, the watercomponent of the inventive herbicidal glyphosate compositions.

Examples of suitable humectants include, without limitation, materialsselected from the group consisting of glycerin, urea, guanidine,glycolic acid and glycolate salts (e.g., ammonium and quaternary alkylammonium), lactic acid and lactate salts (e.g., ammonium and quaternaryalkyl ammonium), polyhydroxy alcohols such as sorbitol, xylitol,inositol, mannitol, pantothenol, glycerol, hexanetriol (e.g.,1,2,6-hexanetriol), 1,4-butanediol, tetramethyl-6-decyne-4,7-diol, PEG-5pentaerythritol ether, polyglyceryl sorbitol, diethylene glycol,propylene glycol, butylene glycol, hexylene glycol and the like,polyethylene glycols, sugars and starches (e.g. sucrose), sugar andstarch derivatives (e.g., alkoxylated glucose, hydrogenated partiallyhydrolyzed polysaccharides and hydrogenated starch hydrolysate),hyaluronic acid, lactamide monoethanolamine, acetamide monoethanolamine,sodium 2-pyrrolidone-5-carboxylate, collagen, gelatin, 10 to 20 moleethoxylates or propoxylates of glucose (e.g., GLUCAM E-20) and mixturesthereof. Preferred humectants include sorbitol, xylitol, inositol,mannitol, pantothenol, glycerol and derivatives and mixtures thereof.

The humectant is preferably added to the glyphosate compositions,including concentrates and tank mixes, in a molar excess to PMIDA, forexample, at a molar ratio to PMIDA of from about 1000:1 to about 1:1,from about 500:1 to about 1:1, from about 250:1 to about 1:1, from about100:1 to about 1:1, from about 50:1 to about 1:1, from about 40:1 toabout 1:1, from about 30:1 to about 1:1, from about 20:1 to about 1:1,from about 15:1 to about 1:1, from about 10:1 to about 1:1, from about5:1 to about 1:1, from about 3:1 to about 1:1 or even from about 2:1 toabout 1:1. The preferred ratio depends on the PMIDA concentration, thehumectant and the relative ability the humectant safening agent tomitigate PMIDA-induced tissue damage and may be readily determined byone skilled in the art using routine experimentation.

It should be understood that in the practice of the present inventionwherein a safening agent is used in a herbicidal glyphosate compositioncontaining PMIDA to mitigate leaf necrosis in the treated cotton plants,the safening agent may comprise any combination of two or more materialsselected from the various classes of safening agents disclosed hereinand including combinations of antioxidants, metal ions, light absorbingcompounds, humectants and/or certain surfactants effective in mitigatingPMIDA-induced necrosis as disclosed in greater detail below. Moreover,it should be understood that many of the specific safening agentsdisclosed herein may be multifunctional and, although identified withina particular class of safening agents, may provide safening againstPMIDA-induced necrosis through one or more mechanisms common to otherclasses of safening agents.

In another embodiment of the present invention, an adjuvant is selectedto control, or moderate, the rate of PMIDA uptake into the cotton plantsuch that the plant can metabolize the PMIDA without development ofsignificant leaf necrosis. Alternatively, the adjuvant can render thePMIDA less biologically active before cellular uptake and translocationof the PMIDA in the plant.

In one embodiment, the adjuvant is a compound having at least twohydroxyl substituents that are oriented no more than 6 atoms apart andin the same spatial orientation within the molecule. Such adjuvantsinclude diols, triols, polyols, and the like, such as alkanediols,alkenediols, alkynediols, benzenediols, dialkanolamines,trialkanolamines, polyalkylene glycols, dialkylene glycols, trialkyleneglycols, and alkylpolyglucosides. Some suitable adjuvants are nonionicsurfactants, such as esters of polyhydric alcohols, alkoxylated amides,alkoxylated alkylphenols, alkoxylated arylphenols, fatty alcoholalkoxylates, alcohol alkoxylates, and alkylpolyglucosides. Commerciallyavailable alkylpolyglucosides include AGRIMUL APG 2067, APG 2069(nonyl/decyl polyglucoside having an average of 1.6 polyglucoside units)and APG 2076 all from Cognis, BEROL AG6202 (2-ethyl-1-hexylglycosidefrom Akzo Nobel) and AL2042 (octyl/decyl with an average of 1.7glycoside units available from Imperial Chemical Industries PCL).

In an embodiment of the invention, the glyphosate composition isformulated such that the weight ratio of the PMIDA uptake-moderatingadjuvant to PMIDA present in the glyphosate composition is selected sothat the rate of transfer of PMIDA into the foliar tissues of the plantis sufficiently low enough to inhibit significant leaf necrosis. Statedanother way, the adjuvant, when applied as part of an aqueous glyphosatespray composition, is of the type and present in a sufficientconcentration to prohibit the crop of transgenic glyphosate-tolerantcotton plants from cellularly uptaking and translocating an amount ofPMIDA thereof sufficient to induce significant leaf necrosis in thecotton plant. One way to accomplish this is to select an adjuvant which,when compared to an equivalent amount by weight of an alkoxylatedalkylamine surfactant (e.g., ethoxylated tallowamine), provides lessintimate contact between the applied herbicidal composition and themicrotopographically rough surface of the cotton plant, for example byincreasing the contact angle of the composition, so as to minimizespreading of the composition into crevices and pores in the plant.Another means for decreasing the rate of PMIDA uptake is to select anadjuvant that minimizes sticking or adhesion to a plant surface whenused in an aqueous spray composition as compared to the same compositioncontaining the alkoxylated alkylamine rather than the selected adjuvant.Yet another way of reducing the rate of PMIDA uptake is to select anadjuvant that causes the spray composition to dry faster, minimizingpenetration through the leaf cuticle relative to the same compositioncontaining the alkoxylated alkylamine rather than the selected adjuvant.These various adjuvant selection strategies may also negatively impactthe herbicidal activity of glyphosate and therefore are preferablyemployed so as to provide a differential effect to obtain the desiredreduction in PMIDA-induced necrosis in the treated cotton plant withoutsignificantly undermining glyphosate herbicidal activity under therelevant growing conditions.

The PMIDA uptake-moderating adjuvant is preferably added to theglyphosate composition at a weight ratio to PMIDA of between about 200:1to 1:1, 150:1 to 1:1, 100:1 to 1:1, 75:1 to 1:1, 50:1 to 1:1, 40:1 to1:1, 30:1 to 1:1, 20:1 to 1:1 or even 10:1 to 1:1. A preferred ratiodepends on the PMIDA concentration, the identity of the adjuvant and therelative ability of that adjuvant to control, or moderate, the rate ofPMIDA uptake into the cotton plant. A preferred ratio may be readilydetermined by one skilled in the art using routine experimentation.

It is to be noted that the present invention encompasses any glyphosateformulation disclosed herein (e.g., concentrate, solid or tank mix)which comprises reduced amounts of PMIDA or any one of the PMIDAsafening agents or safeners described above, as well as any combinationor mixture which includes any one, two, three, four, five or six ofthese safeners. Exemplary combinations are set forth in greater detailin Formulation Tables A-E, below (which illustrate that glyphosate acidand/or salts or other derivatives thereof, can be combined with asafening agent or a reduced amount of PMIDA to form a herbicidalcomposition comprising two to seven components, wherein: G=glyphosate;AO=antioxidant; MI=metal ion; LA=light absorbing compound; H=humectant;CU=adjuvant for mitigating cellular uptake of PMIDA or biologicalactivity of PMIDA; P=reduced amount of PMIDA; and Active No. is aherbicide combination reference number):

TABLE A Glyphosate in Combination with One Safener or a Reduced Amountof PMIDA Active No. Herbicides 1 G + AO 2 G + MI 3 G + LA 4 G + H 5 G +CU 6 G + P

TABLE B Glyphosate in Combination with Two Safeners or One Safener and aReduced Amount of PMIDA Active No. Herbicides 7 G + AO + P 8 G + AO + MI9 G + AO + H 10 G + AO + CU 11 G + AO + LA 12 G + P + MI 13 G + P + H 14G + P + CU 15 G + P + LA 16 G + MI + H 17 G + MI + CU 18 G + MI + LA 19G + H + CU 20 G + H + LA 21 G + CU + LA

TABLE C Glyphosate in Combination with Three Safeners or Two Safenersand a Reduced Amount of PMIDA Active No. Herbicides 22 G + AO + P + MI23 G + AO + P + H 24 G + AO + P + CU 25 G + AO + P + LA 26 G + AO + MI +H 27 G + AO + MI + CU 28 G + AO + MI + LA 29 G + AO + H + CU 30 G + AO +H + LA 31 G + AO + CU + LA 32 G + P + MI + H 33 G + P + MI + CU 34 G +P + MI + LA 35 G + P + H + CU 36 G + P + H + LA 37 G + P + CU + LA 38G + MI + H + CU 39 G + MI + H + LA 40 G + MI + CU + LA 41 G + H + CU +LA

TABLE D Glyphosate in Combination with Four Safeners or Three safenersand a Reduced Amount of PMIDA Active No. Herbicides 42 G + AO + P + MI +H 43 G + AO + P + MI + CU 44 G + AO + P + MI + LA 45 G + AO + P + H + CU46 G + AO + P + H + LA 47 G + AO + P + CU + LA 48 G + AO + MI + H + CU49 G + AO + MI + H + LA 50 G + AO + MI + CU + LA 51 G + AO + H + CU + LA52 G + P + MI + H + CU 53 G + P + MI + H + LA 54 G + P + MI + CU + LA 55G + P + H + CU + LA 56 G + MI + H + CU + LA — —

TABLE E Glyphosate in Combination Five Safeners or Four Safeners and aReduced Amount of PMIDA Active No. Herbicides 57 G + AO + P + MI + H +CU 58 G + AO + P + MI + H + LA 59 G + AO + P + MI + CU + LA 60 G + AO +P + H + CU + LA 61 G + AO + MI + H + CU + LA 62 G + P + MI + H + CU + LA

The safeners as described above can be added to any glyphosate liquidconcentrate, solid concentrate, technical grade glyphosate product,ready-to-use concentrate, or spray composition. Glyphosate is typicallyformulated as a salt in an aqueous liquid concentrate, a solidconcentrate, an emulsion or a microemulsion. Suitable salt forms ofglyphosate which may be used in accordance with any of the formulationsof the present invention include, for example, alkali metal salts, forexample sodium and potassium salts, ammonium salts, di-ammonium saltssuch as dimethylammonium, alkylamine salts, for example dimethylamineand isopropylamine salts, alkanolamine salts, for example ethanolaminesalts, alkylsulfonium salts, for example trimethylsulfonium salts,sulfoxonium salts, and mixtures or combinations thereof. Examples ofcommercial formulations of glyphosate include, without restriction:ROUNDUP ULTRA, ROUNDUP ULTRAMAX, ROUNDUP CT, ROUNDUP EXTRA, ROUNDUPBIOACTIVE, ROUNDUP BIOFORCE, RODEO, POLARIS, SPARK and ACCORD, all ofwhich contain glyphosate as its isopropylammonium salt (IPA); ROUNDUPDRY and RIVAL which contain glyphosate as its ammonium salt; ROUNDUPGEOFORCE, a sodium glyphosate formulation; TOUCHDOWN, a glyphosatetrimesium salt formulation, TOUCHDOWN IQ, a glyphosate diammonium saltformulation, TOUCHDOWN TOTAL IQ, a potassium glyphosate formulation, andROUNDUP WEATHERMAX, a potassium glyphosate formulation.

The relative amount of glyphosate present in a contemplated herbicidalcomposition (i.e., a particulate solid concentrate, or liquidconcentrate, or alternatively a ready-to-use, or tank-mix, composition)may vary depending upon many factors, including for example the weedspecies to be controlled and the method of application. Generallyspeaking, however, the concentration of glyphosate, and optionally asurfactant and/or some other adjuvant or additive (as describedelsewhere herein), in the herbicidal compositions of the invention issufficient to provide at least about 70% control (as determined by meansknown in the art) within about 50 days, preferably about 40 days, morepreferably about 30 days, still more preferably about 20 days, stillmore preferably about 15 days, still more preferably about 10 days,still more preferably about 5 days, and even still more preferably about1 day, or less, after application of the composition to a weed. In amore preferred embodiment, the concentration of glyphosate, andoptionally a surfactant and/or some other additive, in the herbicidalcompositions of the invention is sufficient to provide at least about80%, more preferably at least about 85%, still more preferably at leastabout 90%, and still more preferably at least about 95%, control, ormore, within about 50 days, preferably about 40 days, more preferablyabout 30 days, still more preferably about 20 days, still morepreferably about 15 days, still more preferably about 10 days, stillmore preferably about 5 days, and even still more preferably about 1day, or less, after application of the composition to a weed.

Additionally, the concentration of glyphosate, and optionally asurfactant and/or some other adjuvant or additive (as describedelsewhere herein), in the herbicidal compositions of the invention issufficient to provide at least about 70% control of weed regrowth (asdetermined by means known in the art) for at least about 20, preferablyat least about 30, more preferably at least about 40, still morepreferably at least about 50, still more preferably at least about 60,still more preferably at least about 70, still more preferably at leastabout 80, or even still more preferably at least about 90, days afterapplication of the composition to a weed. In a more preferredembodiment, the concentration of glyphosate, and optionally a surfactantand/or some other adjuvant or additive, in the herbicidal compositionsof the invention is sufficient to provide at least about 80%, morepreferably at least about 85%, still more preferably at least about 90%,or still more preferably at least about 95% control, or more, for atleast about 20, more preferably at least about 30, still more preferablyat least about 40, still more preferably at least about 50, still morepreferably at least about 60, still more preferably at least about 70,still more preferably at least about 80, or even still more preferablyat least about 90, days after application to the weed.

Accordingly, liquid concentrate compositions of the invention areformulated to include glyphosate in a concentration of at least about 50grams, preferably at least about 75 grams, and more preferably at leastabout 100, 125, 150, 175, 200, 225, 250, 275, 300, 310, 320, 330, 340,350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480,490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620,630, 640, 650, 660, 670, 680, 690 or 700 grams (acid equivalent or a.e.)per liter, or more. The glyphosate concentration ranges, for example,from about 50 to about 680 grams (a.e.) per liter, from about 100 toabout 600 grams (a.e.) per liter (gpl), from about 250 to about 600grams (a.e.) per liter, or from about 360 to about 540 grams (a.e.) perliter. When expressed as a weight percentage based on the total weightof the glyphosate concentrate, a liquid concentrate of the inventioncomprises at least about 10 wt. % glyphosate (acid equivalent or a.e.),preferably at least about 15 wt. %, and more preferably at least about20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37,38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55,56, 57, 58, 59, 60, 62, 63, 64, 65, 66, 67, or 68 wt. % a.e., or more.The glyphosate concentration ranges, for example, from about 10 wt. % toabout 70 wt. % a.e., more preferably from about 20 wt. % to about 68 wt.% a.e., and even more preferably from about 25 wt. % to about 45 wt. %a.e. If the concentrate is applied as a ready-to-use composition, theglyphosate concentration is typically from about 1 wt. % to about 3 wt.% a.e., and more preferably from about 1 wt. % to about 2 wt. % a.e.

When expressed as a weight percentage based on the total weight of theglyphosate concentrate, solid concentrate compositions of the inventionare formulated to include glyphosate in a concentration of at leastabout 5 wt. % glyphosate (acid equivalent or a.e.), preferably at leastabout 20 wt. % a.e., and more preferably at least about 25, 30, 35, 40,45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 wt. % a.e., or more. Theglyphosate concentration ranges, for example, from about 5 wt. % toabout 97 wt. % a.e., more preferably from about 30 wt. % to about 85 wt.% a.e., and even more preferably from about 50 wt. % to about 75 wt. %a.e.

Spray compositions of the invention are formulated for application of atleast about 1 gallon of spray composition per acre, preferably at leastabout 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or20 gallons per acre, or more. The spray volume of the spray compositionranges, for example, from about 1 gallon to about 100 gallons per acre,more preferably from about 2 gallons to about 40 gallons per acre, andmore preferably from about 2 gallons to about 5 gallons per acre for anaerial application and from about 5 gallons to about 20 gallons per acrefor a ground application. The glyphosate in such spray compositions isapplied to glyphosate-tolerant transgenic cotton plants at rates of fromabout 0.75 to about 1.125 lb glyphosate a.e./A or about 0.84 to about1.26 kg glyphosate a.e./ha.

Preparation of Glyphosate Compositions

Unless otherwise noted herein, the herbicidal compositions of theinvention that include one or more PMIDA safening agents or safeners canbe prepared on site by the end-user shortly before application to thefoliage of the vegetation to be killed or controlled by mixing in anaqueous solution (i) a glyphosate composition, (ii) a safener, and (iii)any optional components, such as a suitable surfactant or otheradjuvant(s). Such compositions are typically referred to as “tank-mix”compositions. Typically, herbicidal compositions of the presentinvention that are ready to be applied directly to foliage can be madewith a glyphosate concentration as described elsewhere herein. In oneembodiment, an additive composition or mixture is provided for theend-user to provide the PMIDA safener to be added to the tank mix. Theadditive composition or mixture can optionally include surfactant and/orother adjuvant components typical in a glyphosate tank mix, and can beprovided as a liquid or solid. For example, the end-user can be providedwith a sachet of solid material that can be added to the aqueoussolution and mixed to dissolve the material.

Alternatively, the herbicidal compositions of the invention may beprovided to the end-user already formulated, either at the desireddilution for application (i.e., “ready-to-use” compositions) orrequiring dilution, dispersion, or dissolution in water by the end-user(i.e., “concentrate” compositions). Such pre-formulated concentrates canbe liquids or particulate solids.

With respect to the particulate solids, or dry formulations, of thepresent invention, it is to be noted that these may be in the form ofpowders, pellets, tablets flakes or granules. These dry formulations aretypically dispersed or dissolved into water prior to use. Preferably,there are no substantially water insoluble constituents present atsubstantial levels in such formulations such that the formulations aresubstantially water soluble. In dry formulations of the presentinvention, the glyphosate itself may provide the support for otherformulation constituents, or there may be additional inert ingredientswhich provide such support. One example of an inert support ingredientthat may be used in accordance with the present invention is ammoniumsulfate. It will be recognized by one skilled in the art that as usedherein, the term “dry” does not imply that dry formulations of thepresent invention are 100% free of water. Typically, dry formulations ofthe present invention comprise from about 0.5% to about 5% (by weight)water. It is preferred that the dry formulations of the presentinvention contain less than about 1% (by weight) water. Additionally, itis preferred for at least some embodiments that the particulate solidexhibits a dissolution rate of not more than about 5 minutes, about 4minutes, about 3 minutes, about 2 minutes, or even about 1 minute.

Dry, water-soluble or water-dispersible formulations in accordance withthe present invention can be produced by any process known in the art,including spray drying, fluid-bed agglomeration, pan granulation, orextrusion. In dry formulations, glyphosate may be present as a salt, oras an acid. Formulations containing glyphosate acid may optionallycontain an acid acceptor such as an ammonium or alkali metal carbonateor bicarbonate, ammonium dihydrogen phosphate or the like so that upondissolution or dispersion in water by the user a water-soluble salt ofglyphosate is produced.

Also embraced by the present invention are liquid concentrateformulations having an aqueous phase wherein glyphosate is presentpredominantly in the form of a salt, and a non-aqueous phase optionallycontaining a second herbicidal active ingredient that is relativelywater-insoluble. Such formulations illustratively include emulsions(including macro- and microemulsions, water-in-oil, oil-in-water andwater-in-oil-in-water types), suspensions and suspoemulsions. Thenon-aqueous phase can optionally comprise a microencapsulated component,for example a microencapsulated herbicide. In formulations of theinvention having a non-aqueous phase, the concentration of glyphosatea.e. in the composition as a whole is nonetheless within the rangesrecited herein for aqueous concentrate formulations.

It is to be noted that the herbicidal spray compositions of the presentinvention are applied as aqueous solutions or dispersions, whether theyare manufactured ready for application or result from the furtherdilution of a liquid glyphosate concentrate or the addition of water toa particulate solid glyphosate concentrate. However, the term “aqueous,”as used herein, is not intended to exclude the presence of some smallamount of non-aqueous solvent, so long as the predominant solventpresent, is water. Herbicidal spray compositions, also known astank-mixes, typically contain from about 0.5% to about 2% by weight pervolume (w/v) percent glyphosate a.e. and more typically about 1% w/va.e.

Application

Generally speaking, the present invention is additionally directed to amethod of killing or controlling weeds or unwanted vegetation in a fieldcontaining a crop (e.g., of transgenic glyphosate-tolerant cotton plantshaving increased glyphosate tolerance in vegetative and reproductivetissues). In one embodiment, the method comprises the steps of dilutingan aqueous glyphosate concentrate or diluting a solid particulateglyphosate concentrate in a suitable volume of water to form a tank mix,and applying a herbicidally effective amount of the tank mix to foliageof cotton plants genetically transformed to tolerate glyphosate, andsimultaneously to foliage of weeds growing in close proximity to suchplants. This method of use results in control of the weeds or unwantedvegetation while leaving the cotton plants substantially unharmed.

It should be understood that while the present invention is particularlydirected to killing or controlling weeds or unwanted vegetation in acrop of transgenic glyphosate-tolerant cotton plants such as ROUNDUPREADY and ROUNDUP READY FLEX cotton that are susceptible toPMIDA-induced leaf necrosis following over-the-top foliar application ofglyphosate herbicides, the herbicidal glyphosate compositions andmethods of weed control disclosed herein are not limited to suchapplication and may be effectively employed generally in weed managementto kill or control the growth of unwanted vegetation in cultivated croplands as well as in other industrial and residential applications.

The practice of the present invention can be employed to kill or controlthe growth of a wide variety of unwanted plants, including annual andperennial grass and broadleaf weed species, by applying to the foliartissues of the plants aqueous glyphosate compositions of the presentinvention. Particularly important annual dicotyledonous plant speciesinclude, without limitation, velvetleaf (Abutilon theophrasti), pigweed(Amaranthus spp.), buttonweed (Borreria spp.), oilseed rape, canola,indian mustard, etc. (Brassica spp.), commelina (Commelina spp.),filaree (Erodium spp.), sunflower (Helianthus spp.), morningglory(Ipomoea spp.), kochia (Kochia scoparia), mallow (Malva spp.), wildbuckwheat, smartweed, etc. (Polygonum spp.), purslane (Portulaca spp.),Russian thistle (Salsola spp.), sida (Sida spp.), wild mustard (Sinapisarvensis) and cocklebur (Xanthium spp.).

Particularly important annual monocotyledonous plant species that may bekilled or controlled using the compositions of the present inventioninclude, without limitation, wild oat (Avena fatua), carpetgrass(Axonopus spp.), downy brome (Bromus tectorum), crabgrass (Digitariaspp.), barnyardgrass (Echinochloa crus-galli), goosegrass (Eleusineindica), annual ryegrass (Lolium multiflorum), rice (Oryza sativa),ottochloa (Ottochloa nodosa), bahiagrass (Paspalum notatum), canarygrass(Phalaris spp.), foxtail (Setaria spp.), wheat (Triticum aestivum) andcorn (Zea mays).

Particularly important perennial dicotyledonous plant species forcontrol of which a composition of the invention can be used include,without limitation, mugwort (Artemisia spp.), milkweed (Asclepias spp.),Canada thistle (Cirsium arvense), field bindweed (Convolvulus arvensis)and kudzu (Pueraria spp.).

Particularly important perennial monocotyledonous plant species forcontrol of which a composition of the invention can be used include,without limitation, brachiaria (Brachiaria spp.), bermudagrass (Cynodondactylon), yellow nutsedge (Cyperus esculentus), purple nutsedge (C.rotundus), quackgrass (Elymus repens), lalang (Imperata cylindrica),perennial ryegrass (Lolium perenne), guineagrass (Panicum maximum),dallisgrass (Paspalum dilatatum), reed (Phragmites spp.), johnsongrass(Sorghum halepense) and cattail (Typha spp.).

Other particularly important perennial plant species for control ofwhich a composition of the invention can be used include, withoutlimitation, horsetail (Equisetum spp.), bracken (Pteridium aquilinum),blackberry (Rubus spp.) and gorse (Ulex europaeus).

The herbicidal composition of the present invention is applied to plantsat a rate sufficient to give the desired biological effects: control ofweed growth without inducing significant leaf necrosis in cotton plants.These application rates are usually expressed as amount of glyphosateper unit area treated, e.g. grams per hectare (g/ha). What constitutes a“desired effect” varies according to the standards and practice of thosewho investigate, develop, market and use compositions and the selectionof application rates that are herbicidally effective for a compositionof the invention is within the skill of those skilled in the art.Typically, the amount of the composition applied per unit area to give85% control of a weed species as measured by growth reduction ormortality is often used to define a commercially effective rate.

The selection of application rates that are herbicidally effective for acomposition of the invention is within the skill of the ordinaryagricultural scientist. Those of skill in the art will likewiserecognize that individual plant conditions, weather and growingconditions, as well as the specific active ingredients and their weightratio in the composition, will influence the degree of herbicidaleffectiveness achieved in practicing this invention.

The herbicidal spray compositions included in the present invention canbe applied to the foliage of the plants to be treated through any of theappropriate methods that are well known to those having skill in theart, including aerial application, and ground application techniques(e.g., a ground boom, a hand sprayer, rope-wick, etc.).

If desired, the user can mix one or more adjuvants with a composition ofthe invention and the water of dilution when preparing the applicationcomposition. Such adjuvants can include additional surfactant and/or aninorganic salt such as ammonium sulfate with the aim of furtherenhancing herbicidal efficacy.

Optional Formulation Components

Glyphosate formulations typically comprise adjuvants that enhanceglyphosate herbicidal efficacy or otherwise enhance stability of theformulation. For example, glyphosate salts generally require thepresence of a suitable surfactant to optimize uptake into the plant. Asused herein, “surfactant” is intended to include a wide range ofadjuvants that can be added to herbicidal glyphosate formulations toenhance the herbicidal efficacy thereof as compared to the efficacy ofthe glyphosate salt in the absence of such adjuvant. In particular,surfactants facilitate the translocation of glyphosate through the waxyleaf surface and into the plant. The surfactant can be provided in theformulation and/or can be added by the end user to a diluted spraycomposition.

Surfactant classes that have been formulated with glyphosate includecationics, nonionics, anionics, amphoterics, zwitterionics and mixturesthereof. Surfactants typically tending to provide the most usefulglyphosate enhancement are generally, but not exclusively, cationicsurfactants. Examples of cationic surfactant classes include alkylaminealkoxylates (including etheramines and diamines) such as tallowaminealkoxylate, cocoamine alkoxylate, etheramine alkoxylate, tallowethylenediamine alkoxylate and amidoamine alkoxylates; alkylaminequaternary amines such as alkoxylated quaternary alkyl amines (e.g.,ethoxylated quaternary alkyl amines or propoxylated quaternary alkylamines); alkylamine acetates such as tallowamine acetate or octylamineacetate; amine oxides such as ethoxylated amine oxides (e.g.,N,N-bis(2-hydroxyethyl)cocoamine-oxide), nonethoxylated amine oxides(e.g., cetyldimethylamine-oxide) and amidoamine oxides; and quaternaryammonium salts. Suitable cationic surfactants are described, forexample, in U.S. Pat. Nos. 3,853,530, 5,750,468, 5,668,085, 5,317,003and 5,464,807, European Patent No. 0274369, International PublicationNo. WO 95/33379, and U.S. Application Publication No. 2003/0104943 A1,the entire disclosures of which are incorporated herein by reference.

A preferred class of cationic surfactants commonly used in glyphosateformulations is ethoxylated alkylamines of formula (3):

wherein m+n is between about 2 and about 25 and R is a branched orstraight chain alkyl group having from about 12 to about 22 carbonatoms. Preferably, R is a coco or tallow group. Examples of suchalkylamines include TRYMEEN 6617 (from Cognis) and ETHOMEEN C/12, C/15,C/20, C/25, T/12, T/15, T/20 and T/25 (from Akzo Nobel) where “C”indicates R being coco and “T” indicates R being tallow.

Another preferred class of cationic surfactants commonly used inglyphosate formulations are etheramines such as those described in U.S.Pat. No. 5,750,468 including those of the following formulae (4) to (6):

wherein R₁ is a straight or branched chain C₆ to about C₂₂ alkyl, arylor alkylaryl group, m is an average number from 1 to about 10, R₂ ineach of the m (O—R₂) groups is independently C₁-C₄ alkylene, R₃ groupsare independently C₁-C₄ alkylene, and x and y are average numbers suchthat x+y is in the range from 2 to about 60;

wherein R₁ is a straight or branched chain C₆ to about C₂₂ alkyl, arylor alkylaryl group, m is an average number from 1 to about 10, R₂ ineach of the m (O—R₂) groups is independently C₁-C₄ alkylene, R₃ groupsare independently C₁-C₄ alkylene, R₄ is C₁-C₄ alkyl, x and y are averagenumbers such that x+y is in the range from 0 to about 60, and A- is anagriculturally acceptable anion;

wherein R₁ is a straight or branched chain C₆ to about C₂₂ alkyl, arylor alkylaryl group, m is an average number from 1 to about 10, R₂ ineach of the m (O—R₂) groups is independently C₁-C₄ alkylene, R₃ groupsare independently C₁-C₄ alkylene, and x and y are average numbers suchthat x+y is in the range from 2 to about 60.

Examples of preferred nonionic surfactants include alkylpolyglucosides,glycerol esters, ethoxylated glycerol esters, ethoxylated castor oil,ethoxylated reduced sugar esters, polyhydric alcohol esters, ethoxylatedamides, ethoxylated polyethylene glycol esters, ethoxylated alkylphenols, ethoxylated arylphenols, fatty alcohol ethoxylates, ethyleneoxide copolymers, propylene oxide copolymers, organosilicones,fluoro-organics and mixtures thereof.

Examples of preferred anionic surfactants include polyalkoxylatedphosphate esters and diesters; fatty soaps such as ammonium tallowateand sodium stearate; alkyl sulfates such as sodium C₈₋₁₀ alcoholsulfate, sodium oleyl sulfate, and sodium lauryl sulfate; sulfated oilssuch as sulfated castor oil; ether sulfates such as sodium lauryl ethersulfate, ammonium lauryl ether sulfate, and ammonium nonylphenol ethersulfate; sulfonates such as petroleum sulfonates, alkylbenzenesulfonates (e.g., sodium (linear) dodecylbenzene sulfonate or sodium(branched) dodecylbenzene sulfonate), alkylnapthalene sulfonates (e.g.,sodium dibutylnapthalene sulfonate), alkyl sulfonates (e.g., alphaolefin sulfonates), sulfosucinnates such as dialkylsulfosuccinates(e.g., sodium dioctylsulfosuccinate) and monoalkylsulfosuccinate andsuccinamides (e.g., disodium laurylsulfosuccinate and disodiumN-alkylsulfosuccinamate); sulfonated amides such as sodium N-methylN-coco taurate; isethionates such as sodium cocoyl isethionate; N-acylsarcosinates such as N-lauroyl sarcosine, sodium lauryl sarcosinate,sodium cocoyl sarcosinate and sodium myristoyl sarcosinate; andphosphates such as alkylether ethoxylate phosphates and alkylaryletherethoxyated phosphates; saturated carboxylic and fatty acids such asbutyric, caproic, caprylic, capric, lauric, palmitic, myristic orstearic acid; and unsaturated carboxylic acids such as palmitoleic,oleic, linoleic or linoleic acid.

Exemplary amphoteric surfactants include betaines such as simplebetaines (e.g., cocodimethylbetaine), sulfobetaines, amidobetaines, andcocoamidosulfobetaines; imidazolinium compounds such as disodiumlauroamphodiacetate, sodium cocoamphoacetate, sodiumcocoamphopropionate, disodium cocoaminodipropionate, and sodiumcocoamphohydoxypropyl sulfonate; and other amphoteric surfactants suchas alkyl hydroxyethylglycines (e.g., N-alkyl,N,-bis(2-hydroxyethyl)glycine) and alkylaminedipropionates.

A glyphosate formulation of the invention can comprise any combinationof the surfactants described above so long as the surfactant does notinduce significant leaf necrosis in cotton plants when it is formulatedin the glyphosate composition. In one combination described inInternational Publication No. WO 00/15037, an alkylpolyglycosidesurfactant is combined with an alkoxylated alkylamine surfactant. Such asurfactant combination can be used in a glyphosate composition of thepresent invention and applied to transgenic glyphosate-tolerant cottonplants without inducing significant leaf necrosis if the PMIDA contentof the composition is controlled and/or a PMIDA safener is added to theglyphosate composition (e.g., a humectant, metal ions, light absorber,or antioxidant).

Other additives and adjuvants typically employed in glyphosateformulations can be combined with or included in the glyphosatecompositions of the present invention. For instance, urea, ammoniumsulfate, viscosity modifiers, dispersants, organic solvents, glycols,buffers, antifoam agents, di-carboxylic acids and/or polycarboxylicacids are all suitable additives.

Optionally, one or more of the compositions of the present invention mayfurther comprise one or more additional pesticides, such as for example,water-soluble herbicidal active ingredients or water-insolubleherbicidal active ingredients, including without restrictionacifluorfen, asulam, benazolin, bentazon, bialaphos, bispyribac,bromacil, bromoxynil, carfentrazone, chloramben, 2,4-D, 2,4-DB, dalapon,dicamba, dichlorprop, diclofop, difenzoquat, diquat, endothall, fenac,fenoxaprop, flamprop, fluazifop, fluoroglycofen, fomesafen, fosamine,glufosinate, haloxyfop, imazameth, imazamethabenz, imazamox, imazapic,imazapyr, imazaquin, imazethapyr, ioxynil, MCPA, MCPB, mecoprop,methylarsonic acid, naptalam, nonanoic acid, paraquat, sulfamic acid,2,3,6-TBA, TCA, acetochlor, aclonifen, alachlor, ametryn, amidosulfuron,anilofos, atrazine, azafenidin, azimsulfuron, benfluralin, benfuresate,bensulfuron-methyl, bensulide, benzofenap, bifenox, bromobutide,bromofenoxim, butachlor, butamifos, butralin, butroxydim, butylate,cafenstrole, carbetamide, carfentrazone-ethyl, chlomethoxyfen,chlorbromuron, chloridazon, chlorimuron-ethyl, chlornitrofen,chlorotoluron, chlorpropham, chlorsulfuron, chlorthal-dimethyl,chlorthiamid, cinmethylin, cinosulfuron, clethodim,clodinafop-propargyl, clomazone, clomeprop, cloransulam-methyl,cyanazine, cycloate, cyclosulfamuron, cycloxydim, cyhalofop-butyl,daimuron, desmedipham, desmetryn, dichlobenil, diclofop-methyl,diflufenican, dimefuron, dimepiperate, dimethachlor, dimethametryn,dimethenamid, dinitramine, dinoterb, diphenamid, diuron, EPTC,esprocarb, ethalfluralin, ethametsulfuron-methyl, ethofumesate,ethoxysulfuron, etobenzanid, fenoxaprop-ethyl, fenuron, flamprop-methyl,flazasulfuron, fluazifop-butyl, fluchloralin, flumetsulam,flumiclorac-pentyl, flumioxazin, fluometuron, fluorochloridone,fluoroglycofen-ethyl, flupoxam, flurenol, fluridone, flurtamone,fluthiacet-methyl, fomesafen, halosulfuron, haloxyfop-methyl,hexazinone, imazosulfuron, indanofan, isoproturon, isouron, isoxaben,isoxaflutole, isoxapyrifop, lactofen, lenacil, linuron, mefenacet,metamitron, metazachlor, methabenzthiazuron, methyldymron, metobenzuron,metobromuron, metolachlor, metosulam, metoxuron, metribuzin,metsulfuron, molinate, monolinuron, naproanilide, napropamide, naptalam,neburon, nicosulfuron, norflurazon, orbencarb, oryzalin, oxadiargyl,oxadiazon, oxasulfuron, oxyfluorfen, pebulate, pendimethalin,pentanochlor, pentoxazone, phenmedipham, piperophos, pretilachlor,primisulfuron, prodiamine, prometon, prometryn, propachlor, propanil,propaquizafop, propazine, propham, propisochlor, propyzamide,prosulfocarb, prosulfuron, pyraflufen-ethyl, pyrazolynate,pyrazosulfuron-ethyl, pyrazoxyfen, pyributicarb, pyridate,pyriminobac-methyl, quinclorac, quinmerac, quizalofop-ethyl,rimsulfuron, sethoxydim, siduron, simazine, simetryn, sulcotrione,sulfentrazone, sulfometuron, sulfosulfuron, tebutam, tebuthiuron,terbacil, terbumeton, terbuthylazine, terbutryn, thenylchlor,thifensulfuron, thiobencarb, tiocarbazil, tralkoxydim, triallate,triasulfuron, tribenuron, trietazine, trifluralin, triflusulfuron andvernolate.

In one embodiment, a glyphosate concentrate or spray composition isprepared from a manufactured technical grade glyphosate productcomprising at least about 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 wt. %glyphosate acid equivalent (a.e.); less than about 0.05, 0.06, 0.07,0.08, 0.09, 0.10, 0.20, 0.30, 0.40, 0.50 or 0.60 wt. % PMIDA (on an acidequivalent basis); and aminomethylphosphonic acid (AMPA), wherein theweight ratio of PMIDA to AMPA is not more than 0.18:1, 0.19:1, 0.20:1,0.21:1, 0.22:1, 0.23:1, 0.24:1, or 0.25:1, the weight percentages beingon a dry basis. Preferably the glyphosate concentration is at leastabout 95 wt. % on an acid equivalent basis.

In another embodiment, a glyphosate concentrate or spray composition isprepared from a manufactured technical grade glyphosate productcomprising at least about 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 wt. %glyphosate acid equivalent (a.e.); less than about 0.05, 0.06, 0.07,0.08, 0.09, 0.10, 0.11, 0.12, 0.13, 0.14 or 0.15 wt. % PMIDA (on an acidequivalent basis); and a by-product selected from not more than about0.2, 0.3, 0.4, 0.5, 0.6, or 0.7 wt. % N-formyl glyphosate (NFG) or notmore than about 0.01, 0.02 or 0.03 wt. % N-methyl iminodiacetic acid(NMIDA), the weight percentages being on a dry basis. Preferably theglyphosate concentration is at least about 95 wt. % on an acidequivalent basis.

An aqueous herbicidal concentrate composition of the invention, forexample, comprises at least about 360, 370, 380, 390, 400, 410, 420,430, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560,570, 580, 590 or 600 or more grams glyphosate per liter (on an acidequivalent basis), less than about 0.3, 0.35, 0.4, 0.5, 0.6, 0.7, 0.8,0.9, 1, 2, 3, 4 or 5 grams per liter (on an acid equivalent basis) ofPMIDA, and AMPA, wherein the weight ratio of PMIDA to AMPA is not morethan 0.25:1.

In another embodiment, an aqueous herbicidal concentrate compositioncomprises at least about 360, 370, 380, 390, 400, 410, 420, 430, 440,450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580,590 or 600 or more grams glyphosate per liter (on an acid equivalentbasis), less than about 0.3, 0.35, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2,3, 4 or 5 grams per liter (on an acid equivalent basis) of PMIDA, and atleast one surfactant other than an alkoxylated alkyl amine or analkoxylated phosphate ester.

In one embodiment, the glyphosate herbicidal composition in accordancewith the present invention is in the form of an aqueous concentrate andcomprises glyphosate (e.g., N-(phosphonomethyl)glycine or anagronomically acceptable salt thereof), PMIDA, a surfactant componentcomprising a cationic surfactant and a metal ion safening agent whichforms a complex or salt in the composition with PMIDA or an anion formedby deprotonation or partial deprotonation thereof. The molar ratio ofthe metal ion safening agent comprising one or more metal ions to PMIDAacid equivalent is typically at least about 0.4:1, at least about0.45:1, at least about 0.5:1, at least about 0.55:1, at least about0.6:1, at least about 0.65:1, at least about 0.7:1, at least about0.75:1, at least about 0.8:1, at least about 0.85:1, at least about0.9:1 or at least about 0.95:1. Preferably, the concentration PMIDA inthe manufactured technical grade glyphosate product from which suchconcentrates are formulated is managed below about 3000 ppm, morepreferably from about 1200 to about 2500 ppm, such that effectivesafening of the concentrate composition is achieved at molar ratio ofmetal ion safening agent to PMIDA acid equivalent of from about 1:1 toabout 6:1, from about 1:1 to about 5:1, from about 1:1 to about 4:1,from about 1:1 to about 3:1, from about 1:1 to about 2.5:1 andpreferably from about 1:1 to about 2:1.

In such aqueous concentrate formulations, the glyphosate is preferablypredominantly present in the form of an agronomically acceptable salt ofN-(phosphonomethyl)glycine selected from the group consisting of alkalimetal salts, alkylamine salts, and mixtures or combinations thereof. Inaccordance with one especially preferred embodiment, the glyphosate ispredominantly present in the form of the potassium salt and theconcentration of the glyphosate salt is at least about 360, 370, 380,390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520,530, 540, 550, 560, 570, 580, 590 or 600 or more grams per liter on anacid equivalent basis. Examples of preferred cationic surfactantcomponents for use in such concentrates include the ethoxylatedalkylamines of formula (3) and the etheramines of formulae (4) to (6).Preferably, the metal ion safening agent comprises polyvalent iron(e.g., Fe(III)) and may be suitably derived from ferric sulfate andcombined with citric acid as a solubilizing ligand in the concentratecomposition as described above. Alternatively, iron citrate may be usedin the formulation of such iron ion-safened concentrates.

Glyphosate Manufacturing Processes

In a preferred process for the manufacture of glyphosate, an aqueoussolution of N-(phosphonomethyl)iminodiacetic acid (PMIDA) is contactedwith an oxidizing agent in the presence of a catalyst. The catalyst maybe, for example, a particulate activated carbon as described by Chou inU.S. Pat. No. 4,624,937, a noble metal on carbon catalyst as describedby Ebner et al. in U.S. Pat. No. 6,417,133, or a transitionmetal/nitrogen composition on carbon as described in U.S. ApplicationPublication No. U.S. 2004/0010160 A1; International Publication No. WO2005/016519 A1; and in copending and co-assigned U.S. application Ser.No. 11/357,900, filed Feb. 17, 2006, entitled TRANSITIONMETAL-CONTAINING CATALYSTS AND CATALYST COMBINATIONS INCLUDINGTRANSITION METAL-CONTAINING CATALYSTS AND PROCESSES FOR THEIRPREPARATION AND USE AS OXIDATION CATALYSTS, all of which are expresslyincorporated herein by reference.

Conventionally, the oxidation reaction is conducted in one or morestirred tank reactors wherein the catalyst is slurried in an aqueoussolution of PMIDA. The reactor(s) may be operated in either a batch orcontinuous mode. Where reaction is conducted in a continuous mode, theaqueous reaction medium may be caused to flow through a plurality ofcontinuous stirred tank reactors (CSTRs) in series. The oxidizing agentis preferably molecular oxygen, though other oxidants such as, forexample, hydrogen peroxide or ozone, may also be used. Where molecularoxygen is used, the reaction is conveniently conducted at a temperaturein the range from about 70° C. to about 140° C., more typically in therange from about 80° C. to about 120° C. Where a particulate noble metalcatalyst is used, it is typically slurried in the reaction solution at aconcentration of from about 0.5% to about 5% by weight.

In a series of CSTRs, the temperature of each reactor is independentlycontrolled, but typically each reactor is operated in substantially thesame temperature range as the other(s). Preferably, the temperature iscontrolled at a level which maintains glyphosate in solution andachieves substantial oxidation of by-product formaldehyde and formicacid, without excessive formation of either by-product iminodiaceticacid (IDA), which typically results from oxidation of PMIDA, orby-product aminomethylphosphonic acid (AMPA), which typically resultsfrom oxidation of glyphosate. Formation of each of these by-productstends to increase with temperature, with IDA formation occurringprincipally in the first or second reactor where PMIDA concentration ishigh, and AMPA being formed principally in the last or penultimatereactor where glyphosate concentration is relatively high. Where theoxidant is molecular oxygen, it may be introduced independently into oneor more, preferably all, of the series of CSTRs. Typically, the oxygenpressure may be in the range of from about 15 to about 300 psig, moretypically in the range of from about 40 to about 150 psig. Where CSTRsare arranged for cascaded flow without intermediate transfer pumps, thepressure in each successive CSTR is preferably lower than the pressurein the immediately preceding CSTR so as to assure a positivedifferential for promoting forward flow. Typically, oxygen pressure inthe first of a series of CSTRs is operated an a level approximating itspressure vessel rating, while each of the remaining reactors in theseries are operated at a pressure that is within its rating but alsosufficiently below the pressure prevailing in the immediately precedingreactor to ensure forward flow. For example, in a system comprisingthree such reactors in series, the first reactor might be operated at apressure in the range of from about 105 to about 125 psig, the secondreactor at from about 85 to about 100 psig and the third reactor at fromabout 60 to about 80 psig.

A process comprising a series of CSTRs for production of glyphosate isillustrated in FIG. 1. Catalytic oxidation of PMIDA is conducted in aseries of CSTRs 101 to 105 in each of which an aqueous solution of PMIDAis contacted with molecular oxygen in the presence of a particulatecatalyst slurried in the aqueous medium. A reaction slurry exiting thefinal CSTR 105 is directed to a catalyst filter 107 wherein particulatecatalyst is removed for recycle to the reaction system. For recovery ofglyphosate product, filtered reaction solution is divided between avacuum crystallizer 109, typically operated without substantial heatinput (i.e., adiabatically) and an evaporative crystallizer 111 whereinwater is driven off the aqueous phase by transfer heat from a heattransfer fluid such as steam. A crystallization slurry 113 produced invacuum crystallizer 109 is allowed to settle, and the supernatant motherliquor 115, which contains some unreacted PMIDA, is decanted and may berecycled to the reaction system, typically to CSTR 101. A solidtechnical grade glyphosate product may be recovered from the underflowslurry 117 exiting the decantation step. According to the optionalprocess alternative illustrated in FIG. 1, the concentrated vacuumcrystallizer slurry 117 underflowing from the decantation is dividedinto two fractions. One fraction 119 is mixed with the crystal slurryexiting the evaporative crystallizer 111 and directed to a centrifuge121 which separates a solid, crystalline technical grade glyphosate acidproduct that may be used or sold in the form of the solid wet centrifugecake. The other vacuum crystallizer underflow slurry fraction 123 isdirected to another centrifuge 125 which separates a solid crystallineproduct that is used to prepare a concentrated glyphosate salt solution.For this purpose, solids exiting centrifuge 125 are directed to a saltmakeup tank 127 where they are neutralized with a base such as potassiumhydroxide (KOH) or isopropylamine in an aqueous medium to a typicalconcentration of from about 400 to 650 grams per liter, acid equivalent.

Mother liquor 129 from centrifuge 125 typically contains PMIDA in aproportion sufficient to justify recycle thereof to reactor 101. Motherliquor 131 from centrifuge 121 is divided into a purge fraction 133which is removed from the process, and a recycle fraction 135 which isreturned to evaporative crystallizer 111.

In addition to unreacted PMIDA, the reaction solution typically containssmall proportions of other impurities that are innocuous but generallyineffective as herbicides, and which can compromise the crystallizationstep and/or reduce productivity. These must ultimately be removed fromthe process, in part via purge 133 and in part as minor components ofglyphosate products. To balance the proportion of impurities purged infraction 133 with those removed in the concentrated aqueous saltproduct, a mother liquor transfer line 139 is provided for optionaltransfer of mother liquor from line 135 to neutralization tank 127.

FIG. 2 illustrates a modest refinement of the process of FIG. 1 whereinthe crystal slurry exiting evaporative crystallizer 111 is dividedbetween centrifuge 121 and a parallel centrifuge 137. The centrifugewet-cake from centrifuge 121 is removed from the process and may beutilized or sold as a solid technical grade glyphosate product, but thewet-cake from centrifuge 137 is directed to tank 127 for use inpreparing a glyphosate salt concentrate. The mother liquor draining fromboth centrifuges 121 and 137 is combined as stream 131 which is dividedbetween purge stream 133 and stream 135 which is recycled to theevaporative crystallizer.

In operation of the continuous oxidation process depicted in FIGS. 1 and2, a slurry comprising an aqueous solution typically comprising fromabout 6.5% to about 11% by weight PMIDA is introduced continuously intoCSTR 101. The aqueous reaction medium formed in CSTR 101 may typicallycontain from about 2% to about 5% by weight of a particulate noble metalcatalyst suspended therein. For example, the catalyst may comprise abifunctional noble metal on carbon catalyst as described in U.S. Pat.Nos. 6,417,133, 6,603,039, 6,586,621, 6,963,009, and 6,956,005 andpublished U.S. Application Publication No. 2006/0020143, which areexpressly incorporated herein by reference. A source of oxygen, e.g.,air, or preferably oxygen enriched air or substantially pure oxygen, issparged into the aqueous reaction medium within reactor 101 at pressurein the range from about 105 to about 125 psig and reaction is typicallyconducted at a temperature in the range from about 900 to about 115° C.Typically, a PMIDA conversion to glyphosate in the range of about 82% toabout 85% is realized in reactor 101. Reaction solution containingslurried catalyst exiting CSTR 101 flows to second stage CSTR 103 whichis operated under substantially the same temperature conditions as CSTR101, but with oxygen sparged at an oxygen pressure in the range fromabout 85 to about 100 psig. PMIDA conversion achieved at the exit ofreactor 103 is typically in the range from about 90% to about 97% (i.e.,conversion within the second reactor is from about 8% to about 15%,basis, the PMIDA charged to reactor 101).

Reaction solution with slurried catalyst exiting CSTR 103 flows to athird CSTR 105. Oxygen is sparged into reactor 105 at a pressure in therange of from about 60 to about 80 psig. Typically, the temperature ofthe reaction solution in reactor 105 is maintained in substantially thesame range as in reactors 101 and 103. PMIDA conversion in reactor 103is typically 3% to 5%, basis the PMIDA entering reactor 101, resultingin an overall PMIDA conversion in the continuous reaction system fromabout 97% to about 99.5%.

Reactors 101 through 105 are vented under feed back pressure control. Ina preferred mode of operation, the flow rate of oxygen to each reactoris controlled to establish and maintain a target consumption of theoxygen that is introduced into the reactor in the oxidation of PMIDA andreaction by-products such as formaldehyde and formic acid. Theproportionate consumption of oxygen introduced into the reactor isreferred to herein as the oxygen utilization. In conventional operation,the pressure is preferably established at a level that provides anoxygen utilization of at least 60%, preferably at least about 80%, morepreferably at least about 90%. Consistent with the preferred oxygenutilization, the oxygen feed is divided among a series of CSTRsgenerally in proportion to the reaction rate prevailing in each of thereactors. Preferably, the reactors are sized to provide a residence timeeffective to accomplish a substantial fraction of the conversion in thefirst of a series of, e.g., three CSTRs. For example, 65% to 80% of theoxygen may be fed to the first of three reactors, 20% to 30% to thesecond, and 1% to 5% to the third. Typically, reaction in all but thelast of a series of CSTRs is mass transfer limited, i.e., pseudo zeroorder. Under finishing conditions in the last reactor, the reaction isnon-zero order, e.g., approximately first order. As discussedhereinbelow, as the catalyst mass ages, deactivates, conversion may bemaintained by increasing the oxygen flow rates, at the same or differentallocations of oxygen among reactors (e.g., in the process of FIGS. 1and 2 by increasing the proportion of oxygen introduced into reactor 101or 103), to accomplish more of the conversion in the reactors upstreamof the last reactor.

Where the oxygen utilization is relatively high, especially where it isgreater than about 80% or about 90%, it has been found that the PMIDAcontent of the effluent from the final reactor is typically in the rangeof from about 800 to 1300 ppm on a total reaction solution basis. Whereglyphosate is recovered by crystallization from the reaction solution inthe manner described above, the PMIDA content of the glyphosateproduct(s) is generally substantially higher than in the productreaction solution exiting reactor 105. Due to recycle of mother liquorcontaining PMIDA, the aqueous crystallizer feed solutions from whichglyphosate is crystallized generally contain PMIDA in a ratio toglyphosate that is at least 25% higher, or in various steady stateoperations at least 50% higher, than the ratio of PMIDA to glyphosate inthe product reaction solution. The extent of PMIDA buildup is limited bythe volume of purge fraction 133. However, when a process of the typeillustrated in FIGS. 1 and 2 has reached substantially steady stateoperation, a PMIDA range of from about 800 to about 2500 ppm in thefinal reaction solution may typically translate into a concentration of2000 to 6000 ppm in the final glyphosate product, provided that a purgestream is provided in which a reasonable fraction, perhaps up to 10%, ofthe PMIDA contained in the reaction solution is purged from the process.Where more than one form of product is produced (e.g., where product isprovided in both the form of solid technical grade glyphosate productand a concentrated solution of a glyphosate salt) the PMIDA content mayvary between the plural products, depending in part on the direction anddivision of various process streams in the product recovery scheme.

It will be understood that a variety of other schemes may be used forthe preparation of a glyphosate reaction solution by the catalyzedoxidation of a PMIDA substrate and for recovery of a technical gradeglyphosate product(s) from a glyphosate reaction solution in the form ofa solid and/or a concentrated glyphosate salt solution. For example, thefiltered reaction solution may all be directed to an evaporativecrystallizer and the product recovered from the crystallizer slurry in afilter or centrifuge for use either as glyphosate acid or in thepreparation of a concentrated salt solution. In such process, the motherliquor may be divided into a purge fraction and a fraction which isrecycled to the evaporative crystallizer. Alternatively, all or aportion of the mother liquor which is not purged may be recycled to thereaction system. Various oxidation reaction systems for the catalyticoxidation of a PMIDA substrate and alternative process schemes forrecovering technical grade glyphosate product from the oxidationreaction solution, including schemes utilizing adiabatic vacuumcrystallization, are known and described, for example, by Haupfear etal. in U.S. Application Publication Nos. U.S. 2002/0068836 A1 and U.S.2005/0059840 A1, the entire contents of which are expressly incorporatedherein by reference.

Modifications in PMIDA Oxidation Reaction Conditions and Systems

In accordance with the present invention, it has been discovered thatoxygen flow to the reactor(s) may be optionally adjusted in a mannerthat reduces the concentration of PMIDA in the final reaction solution,resulting in a generally proportionate decrease in the PMIDA content ofthe recovered glyphosate product or products. Generally, it has beenfound that increasing oxygen flow in one or more of the reactorsenhances the conversion of PMIDA to glyphosate. The exact relationshipof oxygen flow to PMIDA conversion varies significantly with the otherconditions of the process, with the nature of the catalyst, withcatalyst age and concentration, with batch vs. continuous operation,with product throughput, and with the peculiarities of the configurationa specific reactor, its oxygen feed point, agitation system and gas flowpatterns. However, those skilled in the art can readily adjust theoxygen flow rate for a specific reactor or series of reactors to obtaina desired response in increased conversion of PMIDA. By way of example,where a continuous reaction system of the type illustrated in FIG. 1 isoperating at a residual PMIDA level of 800 to 1500 ppm in the reactionsolution exiting CSTR 105, the PMIDA content of the product reactionsolution may be reduced to from about 150 to about 250 ppm by aproportionate increase in the sum of the oxygen flow rates to reactors101 to 105 of roughly from about 0.1 to about 2% relative to the sum offlow rates that yields a PMIDA content of 800 ppm under otherwiseidentical process conditions. Alternatively, such reduction in PMIDAcontent of the product reaction solution may be achieved by increasingthe flow rate of oxygen to the last of the series of reactors, reactor105, by at least about 5%, typically from about 10% to about 30%relative to the flow rate which yields a PMIDA content of 800 ppm underotherwise identical reaction conditions.

Over an extended period of operations, the catalyst may deactivate tothe extent that desired conversion can no longer be achieved byadjustment of oxygen flow to the last of a series of CSTRs. However, upto a limit defined by useful catalyst life (or at augmentation orpartial replacement with fresh catalyst), the desired conversion canstill be maintained by progressively increasing the oxygen flow to theearlier reactors, e.g., reactors 101 and 103 in FIGS. 1 and 2.Preferably, the oxygen flow rate is increased sufficiently to actuallyincrease the conversion in the reaction solution exiting the penultimatereactor, so that the duty imposed on the last reactor is reduced. Thus,the desired ultimate conversion is obtained even though the productivityof the last reactor per se has declined. Conversion can also beincreased by increasing residence time in the reactors. As those skilledin the art will appreciate, an infinite number of combinations of flowrates to the respective reactors may be available to achieve the desiredlevel of PMIDA in the product reaction solution.

It has further been discovered that maintaining a desired PMIDA contentin the reaction solution exiting the final reactor can be facilitated byselection of the system for monitoring the composition of the reactionsolution. In a particularly preferred embodiment of the invention, thecomposition of the reaction solution exiting the final reactor ismonitored by passing the reaction solution, or a sample of suchsolution, through a device of the type described in co-assigned U.S.provisional application Ser. No. 60/667,783, filed Apr. 1, 2005,entitled CONTROL OF PMIDA CONVERSION IN MANUFACTURE OF GLYPHOSATE. Forexample, the conversion can be estimated by cumulative heat generationarising from the oxidation of PMIDA, by the instantaneous rate of heatgeneration, or combination of both. From the instantaneous rate, theconversion and rate constant may also be inferred in the mannerdescribed in the aforesaid application, particularly if analyzed incombination with laboratory kinetic data and historical operationalprocess data. Other methods for monitoring conversion include measuringthe cumulative or instantaneous oxygen consumption, and/or thecumulative and/or instantaneous rate of carbon dioxide generation,and/or a function of the power consumed in maintaining a select currentdensity, or a select potential difference between electrodes immersed inthe reaction solution. A device useful for the latter purpose comprisesa pair of electrodes immersed in the reaction solution or a samplethereof, and is controlled to maintain a select current density orimpose a select voltage or schedule of voltages between the electrodes.In the latter instance, the device typically comprises a third electrodefunction as a reference electrode for use in maintaining the desiredvoltage. Where the device is controlled to maintain a select currentdensity, the voltage required to maintain the current is indicative ofthe residual PMIDA content in the solution. As long as PMIDA is present,and the current is established at a level sufficient to consume C₁s suchas formaldehyde and formic acid, the requisite voltage may approximatethat required for the electrochemical oxidation of PMIDA. As PMIDA isexhausted, the voltage increases to a level effective forelectrochemical oxidation of glyphosate. Where a select voltage orschedule of voltages is applied, the current observed at a voltageeffective for electrochemical oxidation of PMIDA is indicative ofresidual PMIDA content. In the process of FIGS. 1 and 2, such anelectrochemical oxidation probe is conveniently located in the streamexiting the catalyst filter 107, preferably following a polishing filterdownstream of the catalyst filter which is effective for removal ofcatalyst fines.

In a further advantageous embodiment of the process of the invention,cumulative or instantaneous heat generation, oxygen consumption, orcarbon dioxide generation, or an electrochemical oxidation probe aremonitored and used to estimate the conversion in and/or composition ofthe reaction solution exiting the next to last reactor (reactor 103 inFIGS. 1 and 2), and/or the third last reactor (i.e., reactor n−2 in aseries of n reactors; e.g., reactor 101 in FIGS. 1 and 3). Where anelectrochemical oxidation probe is used in the third last reactor, it ispreferably operated to maintain a target current density. Byperiodically reversing the polarity, the electrodes are kept clean inthe catalyst slurry environment. Optionally, further intelligence forcontrolling PMIDA levels exiting the reaction system may be provided byapplication of mathematical models which project conversions based oninput of current process signals into a program based on firstprinciples and/or historical operating data. By these means, the processoperator, or a process management control system, can increase theoxygen flow to the earlier reactor or reactors as the catalyst massdeactivates, thereby reducing the demand on the final reactor andachieving the desired conversion and residual PMIDA content in thesolution exiting the last reactor.

In a batch reaction system, the PMIDA content of the reaction solutionmay optionally be reduced by extending the cycle during which a sourceof oxygen is sparged into the aqueous reaction medium. For a givenoperation, a conventional oxygen flow cycle may be identified by anyconvenient conventional means, as, for example, by periodic analysis ofsamples from the reactor. Where performance as a function of time isreasonably consistent, timing of the batch may be sufficient andsampling may not be necessary. In any case, it has been discovered that,by extending the oxygen sparging cycle by from about 2 to about 15minutes, more typically from about 5 to about 10 minutes, PMIDAconversion can be increased to reduce residual PMIDA content from arange from about 275 to about 350 ppm to a range from about 50 to about100 ppm or even lower.

Because the oxidation reaction is exothermic, means are provided fortransfer of reaction heat from the reaction mixture in the reactor(s)under feedback temperature control. Thus, if a cooling fluid such ascooling tower water is passed through a heat exchanger (e.g., coolingcoils) for controlling the reaction temperature, the extent of reactioncan be estimated from the cumulative heat dissipation over the batchcycle, as may be determined from an integrated average of the product ofcooling fluid flow rate and temperature rise through the heat exchangerduring the course of the batch. Since the oxidation reaction is betweenzero order and first order for PMIDA (Langmuir-Hinshelwood kinetics),and the first order region is generally below 1000 ppm PMIDA, theresidual PMIDA content may also be inferred from the residual rate ofreaction at the end of the batch. As the catalyst ages and its activitydeclines, the effect on first order rate constants can be periodicallytracked by sampling near the end of the batch. In operation of a batchprocess, the rate and extent of catalyst deactivation may be monitoredby keeping track of “oxygen practice,” as measured by the ratio toglyphosate produced of cumulative quantity of oxygen used to reach thetarget conversion. This index, which may be expressed in kg oxygen permetric ton of glyphosate (or alternatively in lbs. per hundredweight),increases as the catalyst deactivates for a given PMIDA payload. Asimilar index may be used for a series of CSTRs, but at higher startingand ending values.

The achievement of a low PMIDA content in the filtered aqueous reactionproduct stream by increased oxygen flow or extended batch cycletypically involves a modest penalty in glyphosate yield and an increasein the concentration of certain impurities, prominentlyaminomethylphosphonic acid (AMPA). Where a noble metal on carboncatalyst is used for the reaction, these schemes may also typicallyresult in an increased rate of deactivation of catalyst, resulting inincreased catalyst consumption. However, the reduced PMIDA contentgenerally affords a benefit in the preparation of herbicidal glyphosatecompositions for the control of weeds in genetically-modified cottoncrops that outweighs the adverse effects on yield, catalyst consumptionand the minor increase in impurities.

In accordance with the invention, several additional modifications tothe oxidation reaction system have been identified that can be used inlieu of, or in combination with increased oxygen flow and/or extendedbatch cycle as described above.

Alternatively, or in addition to increasing oxygen flow to thereactor(s), enhanced conversion of PMIDA can be achieved by operation atrelatively high reaction temperature within the aforesaid range of fromabout 70° to 140° C., and/or by modification of the catalyst system.

Conversion of PMIDA is promoted by operation at elevated temperature(e.g., in the range of about 110° C. or above) typically from about 110°to about 1.25° C. Because higher temperature leads to increasedby-product formation, such as by oxidation of glyphosate to AMPA, thetemperature is preferably not increased to more than the extent that maybe necessary, either alone or in combination with other modificationssuch as oxygen flow rate, to achieve the target level of PMIDA. Asignificant effect on PMIDA conversion can be achieved by operation inthe range of from about 115° to about 125° C., or perhaps optimally inthe range of from about 118° to about 125° C.

The catalyst system may be modified by an increased charge of noblemetal on carbon catalyst, by adding activated carbon to the catalystsystem, and/or by altering the selection of promoter for the noble metalon carbon catalyst. If a fresh catalyst charge is increased beyond athreshold level (e.g., above a concentration in the range of from about1.5% to about 2% by weight) the effect may be to increase the oxidationof PMIDA to IDA rather than glyphosate. However, while PMIDA may oxidizeto IDA resulting in an overall selectivity loss, the net effect is stillto reduce the PMIDA content of the final glyphosate product. Moreover,when a catalyst mass has been used through a substantial number ofrecycles, activity of the catalyst mass may usefully be increased bypurging some fraction of the spent catalyst and adding fresh catalyst inits place. When this method is followed, PMIDA conversion may besignificantly enhanced without significant formation of IDA (i.e.,selectivity to glyphosate may be substantially preserved).

An activated carbon catalyst such as the catalyst that is described byChou in U.S. Pat. No. 4,624,937, is highly effective for oxidation ofPMIDA to glyphosate, even if not as effective for oxidation ofby-product C₁ species such as formaldehyde and formic acid. The carboncatalyst is also relatively inexpensive compared to the noble metal oncarbon catalyst, though it is typically consumed at a substantiallyhigher rate. Thus, a fairly liberal addition of carbon catalyst toeither a batch reactor, or to the last of a series of cascaded CSTRs,(e.g., in a proportion of at least about 1.5% by weight, typically fromabout 2.5% to about 3.5% by weight, basis, the noble metal on carboncatalyst charge) can materially reduce the residual PMIDA content in thefinal reaction solution.

Certain transition metals such as Bi and Te are effective as promotersto improve the effectiveness of a noble metal on carbon catalyst foroxidation of by-product C₁ species such as formaldehyde and formic acid.However, data indicate that the oxidation of PMIDA may be marginallyretarded by such promoters, perhaps by directing oxygen to contact andreact with C₁ species in preference to PMIDA. When used either alone orin combination with activated carbon for preparation of low PMIDAcontent glyphosate, a noble metal on carbon catalyst can either have nopromoter, or have a promoter whose identity and loading is selected tominimize any negative effect on the kinetics of the PMIDA oxidation. Inthis connection, a particular reactor, such as the final reactor in aseries of CSTRs, can be dedicated to substantial extinction of PMIDA,and the use of a catalyst which has no promoter, or in which thepromoter is selected to be favorable to PMIDA oxidation, can be limitedto the dedicated reactor.

Because further thermal effects are minimal once a relatively highconversion has been achieved, a finishing reactor, such as the finalreactor in a series of continuous reactors, can readily be operated as aflow reactor (e.g., with a fixed catalyst bed) rather than a back-mixedreactor, so as to enhance the driving force for extinction of PMIDA.Moreover, such finishing reactor can be added, for example, as reactorn+1 after a series of n CSTRs, for example as the fourth reactorfollowing reactor 105 of FIG. 1. Optionally, the catalyst loaded in suchreactor can predominantly or exclusively comprise activated carbon.

In order to minimize residual PMIDA in the product reaction solutionexiting the final stage of a cascaded continuous stirred tank reactionsystem, it is helpful to minimize short circuiting of aqueous mediumfrom the reactor inlet to the reactor exit. Thus, in accordance withprinciples known to the art, the feed point, exit point, baffle array,agitation pattern and agitation intensity may be selected to minimizethe extent of short circuiting. Where a CSTR is provided with anexternal heat exchanger through which the reaction mixture is circulatedfor removal of the heat of reaction, the reaction mixture mayconveniently be withdrawn from the reactor at a forward flow port in thecirculating line. Advantageously, the inlet for reaction medium can bepositioned in the same circulating line downstream of the exit port by adistance sufficient to avoid any short circuiting due to axialbackmixing. For example, the exit port can be placed in the circulatingline upstream of the heat exchanger and the inlet port can be locatedimmediately downstream of the heat exchanger.

In accordance with the invention, further process modifications outsidethe principal PMIDA oxidation system, may be used to reduce the PMIDAcontent of the finished glyphosate product(s). Such additionalmodifications, as described hereinbelow, may be used together with orlieu of any combination of the modifications to the reaction system thatare described above.

PMIDA Purge

For example, in the process of FIG. 1, the volume of purge streamfraction 133 can be increased relative to evaporative crystallizermother liquor recycle fraction 135, thus reducing the steady stateinventory of PMIDA in the glyphosate product recovery area of theprocess. The extent of purge required to obtain a given specificationfor a given form of glyphosate product varies depending on the PMIDAcontent of the filtered reaction product stream and the exact materialbalance of the overall process, and especially the material balance ofthe glyphosate recovery area. The effect of increased purge may beaugmented by a more extended wash of the separated glyphosate solidsthat are obtained as a centrifuge wet-cake in centrifuges 121 and 125,or in filters or centrifuges that may be used in alternative schemes forproduct recovery. Increased wash volume is ordinarily integrated withthe purging scheme because either the wash liquor itself must be purged;or, if the wash liquor is combined with one or more of the recyclemother liquor streams, it marginally increases the amount of PMIDA thatmust be purged from the process. In either case, the net purge volume isgenerally increased by an increment corresponding to the volume of thewash liquor. An increase of wash volume might be achieved independentlyof the purge fraction where the quality of the wash solution permits itsuse in preparing the aqueous solution of PMIDA which is introduced intothe reaction system.

Allocation of PMIDA Among Plural Grades of Glyphosate

The processes as illustrated in FIGS. 1 and 2 are also adapted for theproduction of different grades of glyphosate, e.g., one grade that has aPMIDA content less than 600 ppm for use in glyphosate compositions forapplication to genetically-modified cotton crops to inhibitPMIDA-induced necrosis, and another grade of higher PMIDA content thatis quite satisfactory for multiple other applications. Generally, thecentrifuge wet-cake produced in centrifuge 125 has a lower PMIDA contentthan the wet-cake produced in centrifuge 121 (or 137) because the motherliquor from the vacuum crystallizer is less concentrated than the motherliquor from the evaporative crystallizer, and because no recycle motherliquor stream is introduced into vacuum crystallizer 109. The PMIDAcontent of the solid glyphosate acid product removed from the process bycentrifuge 121 can be balanced with the PMIDA content of the saltconcentrate exiting the process from neutralization tank 127 byincreasing the fraction of vacuum crystallizer slurry underflow 117 fromthe decantation step that is directed to evaporative crystallizercentrifuges 121 relative to that which is directed to centrifuge 125and/or by increasing the fraction of evaporative crystallizer slurrythat is directed to centrifuge 137 for production of evaporativecrystallizer centrifuge wet-cake to be incorporated into theconcentrated glyphosate salt solution in salt makeup tank 127. Ifdesired, the PMIDA content can be unbalanced, and a disproportionatelylow PMIDA content salt concentrate prepared by minimizing the fractionof vacuum crystallizer slurry 117 directed to centrifuge 121, andtransferring mother liquor from the evaporative crystallizer circuit tothe neutralization tank via mother liquor transfer line 139 and/or byeliminating the fraction of evaporative crystallizer slurry that isdirected to centrifuge 137.

Alternatively, a low PMIDA content solid glyphosate acid product can beprepared by diverting PMIDA to the salt makeup tank 127. In this case, arelatively high fraction of the vacuum crystallizer slurry underflowingthe decantation step is directed to centrifuge 121, and a high fractionof the evaporative crystallizer slurry is sent to centrifuge 137.According to these various process schemes, the process material balancecan be managed to contemporaneously, or indeed simultaneously, toproduce two separate glyphosate products of distinctly differentglyphosate basis PMIDA content.

As a further alternative to the preparation of low PMIDA contentglyphosate product, the product obtained during process startup can besegregated and dedicated for use in glyphosate composition forapplication to and weed control in genetically-modified cotton crops. Bystarting up with water in the evaporators, neutralization tank andprocess storage vessels (not shown), the impact of PMIDA in recyclemother liquor can be avoided immediately after startup, and kept to amodest level during the early portion of the transient period in whichthe product recovery area gravitates to steady state operation.

Further alternative process schemes for allocating residual PMIDA amongtwo or more glyphosate products are described by Haupfear et al. in U.S.Application Publication No. U.S. 2005/0059840 A1, the entire text ofwhich is expressly incorporated herein by reference.

Whether by sequential operation, segregated operations, or control ofprocess material balance to simultaneously yield different gradeproducts, the processes of the invention can be implemented to yield aplurality of differing grade products, including a low PMIDA producthaving a glyphosate basis PMIDA content typically less than about 1000ppm, preferably less than about 600 ppm, and at least 25% lower than atleast one other, or preferably any other, of such plurality. Moreover,using any one or more of the various process stratagems described above(or below), a low PMIDA product may be produced having a glyphosatebasis PMIDA content that is less than about 1000 ppm, or less than about600 ppm, and at least about 50% lower, or even at least about 75% lower,than the PMIDA content of another of the plurality of products, orpreferably any such plurality.

Ion Exchange

In a further alternative embodiment of the invention, PMIDA may beremoved from one or more process streams by ion exchange. A variety ofoptions may be followed in providing for removal of PMIDA by ionexchange. For example, an ion exchange column could be used to removePMIDA from mother liquor as it is recycled from the evaporativecrystallizer centrifuge 121 (and/or 137) before separation of purgefraction 133, or in recycle mother liquor fraction 135 after separationof the purge fraction, or in stream 129 from centrifuge 125.Alternatively, or additionally, an ion exchanger could be positioned inthe filtered reaction solution stream ahead of the point where it isdivided between the vacuum crystallizer 109 and the evaporativecrystallizer 111 in FIG. 1.

In an ion exchanger, the PMIDA-bearing process stream is contacted withan anion exchange resin, preferably an anion exchange resin that has agreater affinity for the more strongly acidic PMIDA anion than for therelatively more weakly acidic glyphosate anion and for many of the othercompounds in this stream. Because the process stream from which PMIDA isto be removed typically has a high ratio of glyphosate to PMIDA, theresin's affinity for PMIDA should be significantly greater than itsaffinity for glyphosate. Efficient separation of PMIDA is enhanced wherethe affinity of the resin for PMIDA is at least two times, three times,four times, five times, 10 times, 20 times or as much as 100 times itsaffinity for glyphosate. Weakly basic exchange resins are preferred.Functional sites of conventional weak base anion exchange resinstypically comprise secondary amine or tertiary amines. Available anionexchange resins typically comprise, for example, a styrene butadienepolymer having a secondary or tertiary amine site which may beprotonated in acidic solution to function as an anion exchanger.Suitable commercially available resins include, for example: AMBERLYSTA21, AMBERLITE IRA-35, AMBERLITE IRA-67, AMBERLITE IRA-94 (all from Rohm& Haas, Philadelphia, Pa.), DOWEX 50 x 8-400 (Dow Chemical Company,Midland, Mich.), LEWATIT MP-62, IONAC™ 305, IONACM 365 and IONAC™ 380(Sybron Chemicals, Birmingham, N.J.), and DUOLITE a-392 (DiamondShamrock Corp., Dallas, Tex.).

A complication in removal of PMIDA by ion exchange can arise from thepresence of a substantial fraction of chlorides in the filtered reactionsolution, which tend to be concentrated somewhat in the solutionultimately subjected to ion exchange such as evaporative crystallizermother liquor 131. When an acidic solution such as mother liquor recyclesolution 131 is passed over an anion exchange resin, chloride ions areretained at the protonated amine sites preferentially to PMIDA. Wherethis is the case, two columns may typically be provided in series, withthe first column dedicated to removal of chloride ions, with either astrong or weak base anion exchange resin, and the effluent from thefirst column passed through a second column comprising a weak baseexchange resin wherein PMIDA anions are removed. Each column may beeluted and the anion exchange resin regenerated by passage of a causticsolution, typically sodium hydroxide (NaOH), through the column.

The solution from which PMIDA and/or chlorides are to be removed ispassed through the column in which the desired exchange occurs untilbreakthrough of the ion to be removed is observed in the effluent fromthe column. Breakthrough may occur when the entire column has reached anequilibrium level of chloride ion or PMIDA as the case may be. Assaturation is approached, the capacity of the column for the targetanion may be reduced to some extent by the presence of the anions ofcomponents that are of comparable acidity as the target anion, e.g.,phosphate and N-formylglyphosate (NFG). Breakthrough may be determinedby any conventional means of detection, including, for example,conductivity, absorbance of light (254 nm), pH and the like. In apreferred method, PMIDA breakthrough is detected by monitoringconductivity of the column eluate. For example, as described in U.S.provisional application Ser. No. 60/667,783, a potential may be appliedbetween a working electrode and another electrode immersed in the columneluate or a sample thereof, and measurement made of a function of thepower consumed in maintaining a select current density, or a selectpotential difference between the electrodes. Alternatively, the endpoint of an ion exchange cycle can be practiced by volumetric control ofthe quantity of aqueous solution passed through the column (i.e., thecumulative quantity of mother liquor or other PMIDA-containing streampassed through the anion exchange bed relative to the volume of the bed,typically expressed in “bed volumes.”).

After an ion exchange cycle is complete, the column can be eluted toremove the anion that has been collected therein.

A column in which chlorides have been collected from a process streammay be eluted with a caustic solution (e.g., NaOH) to regenerate freeamine sites and produce an eluate salt solution that may typically bediscarded. Interstitial caustic is removed by washing the column withwater. Unless interstitial caustic is removed, it is recycled to thecrystallizer with adverse impact on the crystallization.

A column in which PMIDA has been collected from a process stream mayfirst be washed with water to displace process liquid from the column.Thereafter, the column may be eluted with a strong acid to remove PMIDAfor recovery; and then regenerated, typically with a caustic solutionsuch as NaOH, and then washed with water to remove interstitial caustic.Eluate comprising PMIDA can be recycled to the oxidation reaction systemfor further conversion of the PMIDA to glyphosate. Illustrative examplesof acids that can be used for elution of PMIDA from an ion exchangecolumn include strong mineral acids such as hydrochloric acid orsulfuric acid. In various embodiments, the ion exchange resin may becontacted with a wash solution or multiple wash solutions during aseries of wash steps subsequent to elution. Suitable wash solutionsinclude, for example, water, a buffer solution, a strong base such asKOH, NaOH, or NH₄OH or a weaker base such as Na₂CO₃.

During elution of an ion exchange column loaded with PMIDA, the columneffluent is monitored for the conjugate base of the strong acid (e.g.,chloride ion when Cl is detected in the effluent). Upon appearance ofchlorides, recycle of eluate to the PMIDA oxidation step is terminated,and the column is washed with water, then caustic and then again waterto return it to the free amine state. If desired, buffers and/orsolvents may be used in washing of the column after elution, but this isnot ordinarily necessary or useful.

Ion exchange can be conducted at ambient or elevated temperature. Moreparticularly, the mother liquor from the evaporative crystallizercentrifuge 121 (and/or 137) may be treated by ion exchange resin withoutheating or cooling prior to introduction into the ion exchange column.Typically, this stream has a temperature in the range of from about 45°to about 85° C., more typically from about 55° to about 75° C. Columndimensions and flow rates through the column are governed by standardcolumn design principles and can be readily determined by one skilled inthe art.

If desired, a third column can be provided downstream of the PMIDAcolumn for recovery of glyphosate by ion exchange. See, for example, theprocess as described in U.S. Pat. No. 5,087,740, which is expresslyincorporated by reference herein.

In various embodiments, a still further ion exchange column may beprovided for recovery of platinum or other noble metal that may havebeen leached from the catalyst used in the oxidation of PMIDA. Such aprocess for recovery of noble metal by ion exchange is described incopending and co-assigned U.S. application Ser. No. 11/273,410, filedNov. 14, 2005, entitled RECOVERY OF NOBLE METALS FROM AQUEOUS PROCESSSTREAMS, which is also expressly incorporated herein by reference.Preferably, ion exchange for recovery of noble metal is conductedupstream of the ion exchanger used for separation of PMIDA or removal ofchlorides.

In a continuous process such as that illustrated in FIG. 1, a pair ofion exchange columns can be provided in parallel for each ion exchangeoperation that is conducted as part of the process. In this manner, onecolumn can be used for removal of target anion while the other is beingeluted and regenerated.

Although ion exchange has been described above with reference to ionexchange columns, the resin may alternatively be added directly withagitation as a solid phase reagent to the process stream from which thePMIDA (or other target anion) is to be removed. Ion exchange operationshave been described above with reference to the continuous processesdepicted in FIGS. 1 and 2. Removal of excess PMIDA by ion exchange isalso useful in a simplified glyphosate product recovery scheme in whichall product reaction solution is directed to a single glyphosaterecovery stage such as a single evaporative crystallizer. A singlecrystallizer typically may be used where the oxidation reaction isconducted in a batch mode. In such a process, glyphosate crystals areseparated from the crystallization slurry by filtration orcentrifugation, and the mother liquor typically recycled to thecrystallizer. In extended operations, a fraction of mother liquor ispurged to remove impurities. Ion exchange for removal of PMIDA from themother liquor allows reduction of the purge fraction necessary toprovide a given PMIDA specification in the glyphosate product. Also, thePMIDA which is removed can be recovered by elution as described aboveand recycled to the oxidation reactor.

FIG. 3 illustrates an exemplary ion exchange system, located, forexample, in stream 131 of FIG. 1 or 2, upstream of the purge 133. Asillustrated, the system comprises three columns in series, a platinum(or other noble metal) recovery column 201, a chloride removal column203 and a PMIDA removal column 205. Column 201 comprises an adsorptionzone which may comprise activated carbon, or more typically a weak baseanion exchange resin, strong base anion exchange resin, strong acidcation exchange resin weak acid cation exchange resin, chelating resin,or in some instances, mixtures thereof. Specific resins useful in therecovery of solubilized platinum are described in U.S. Ser. No.11/273,410, expressly incorporated herein by reference. Preferably, achelating resin is used. Column 203 comprises an anion exchange zonecontaining a resin of the type described hereinabove for removal ofchlorides, and column 205 comprises an anion exchange zone containing aresin of the type described for the removal of PMIDA.

Although only a single column is depicted for each recovery or removaloperation in FIG. 3, typically at least a pair of columns is provided inparallel at each stage to allow one column to be eluted, regenerated,and washed while the other is in operation for removal of Pt, Cl⁻ orPMIDA, respectively. Operating conditions for column 201 are describedin U.S. Ser. No. 11/273,410. As further described in the '410application, breakthrough of noble metal from column 201 may be detectedby ICP-MS, ICP-OES, or AA. A simple conductivity device is effective fordetermining breakthrough of chlorides from column 203 or 205.

While FIG. 3 depicts separate columns (or column pairs) in series forchloride removal and PMIDA removal, respectively, the two columnsfunction as a single adsorption system so far as adsorption phenomenaare concerned, at least in the case where the ion exchange properties ofthe resins used in columns 203 and 205 are substantially the same. Inany case, all adsorbable components of the solution are initiallyadsorbed on column 203 but PMIDA is progressively displaced by Cl⁻ asthe column becomes loaded. PMIDA desorbed from or passing through column203 is adsorbed on the anion exchange resin in column 205. When column203 (or a corresponding adsorption zone within a single column) becomesloaded with chloride, the latter ions eventually break through in theeffluent from column 203 (or corresponding zone) and begin displacingthe PMIDA from column 205 (or a corresponding downstream adsorption zoneof a single column). Separating the adsorption bed into two columnsfacilitates monitoring the chloride wave and scheduling regeneration ofanion exchange resin for sustained operations. Breakthrough from column205 may result from either saturation of the resin therein with PMIDA ordisplacement of PMIDA by chloride. In either case, breakthrough mayoccur before maximum PMIDA loading is realized, with the PMIDA contentof the effluent progressively increasing as column saturation isapproached, rising to the level in the inlet mother liquor stream whensaturation is reached. Where chloride displaces PMIDA, the PMIDA loadingreaches a maximum and then begins to decline as it is displaced bychloride. In the system depicted in FIG. 3, this conditions can beavoided if column 203 is regenerated as soon as chloride breakthrough isobserved. In either case, process operators can identify an optimumbalance between PMIDA removal efficiency and column loading.

Regardless of whether the chloride and PMIDA ions are removed inphysically separate adsorption beds in series or in a single adsorptionbed, the adsorption system may be considered to comprise two distinctadsorption zones, one in which chlorides are being adsorbed and anotherin which PMIDA is being adsorbed. However, the size and location ofthese adsorption zones are not static. The boundary between the zonesmoves as the chloride wave advances in displacing PMIDA from the resin.

Shown at 207 is a device effective to sense breakthrough of PMIDA fromcolumn 205. The device comprises a pair of electrodes immersed in thestream exiting the column or a sample thereof, and is controlled tomaintain a select current density or impose a select voltage or scheduleof voltages between the electrodes. Where the device is controlled tomaintain a select current density, breakthrough of PMIDA is reflected ina drop, typically a relatively sharp drop in the voltage required tomaintain the select current density. Where a select voltage, orprogrammed series of voltages is imposed, breakthrough of PMIDA isindicated by a significant increase in current at a voltage that issufficient for electrolytic oxidation of C₁s and PMIDA but not residualglyphosate. Detailed descriptions of devices which function on thesebases are set forth in co-assigned U.S. provisional application Ser. No.60/667,783, which is expressly incorporated herein by reference.

Whenever any of columns 201, 203 or 205 reaches a breakthroughcondition, introduction of mother liquor is terminated and the adsorbedcomponent recovered. In the case of column 205, PMIDA may be eluted witha strong acid such as HCl. Both columns 203 and 205 may be regeneratedusing a caustic eluant, followed by a water wash, as described above.The aqueous NaCl eluate may be discarded. In the case of column 201, thenoble metal component may optionally be eluted with an eluant, e.g., anacidic eluant where the noble metal species is present in the form ofcation, or a caustic eluant where the noble metal is present in ananion. However, in the case of column 201, more quantitative recoverycan generally be achieved by removing the loaded resin from the column,incinerating the resin, and recovering noble metal from the ash.

Recovery of noble metal in column 201 is typically in the range betweenabout 60% and about 85%. Thus, in monitoring operation of this column“breakthrough” is a relative term, and the breakthrough detection deviceis calibrated to detect an increase in signal above a steady statelevel. In any event, a portion of the noble metal is typically lost inpurge stream 133 or in the product glyphosate salt concentrate. WherePMIDA is removed by ion exchange via column 205, it has been found thata portion of the noble metal passing through columns 201 and 203 isadsorbed on the resin contained in column 205. If this column isregenerated or washed with aqueous ammonia, the platinum is desorbed,and ultimately lost either in the purge stream or by incorporation intothe aqueous glyphosate salt product. However, it has been discoveredthat if the column is regenerated with a strong base such as an alkalimetal hydroxide, e.g., NaOH or KOH, and washed with strong base orwater, platinum species are typically not desorbed, but remain on thecolumn, thus allowing ultimate recovery of this fraction of the platinumby removal and incineration of the resin.

Disposition of the eluates from columns 203 and 205, respectively, is asdescribed above. The acidic eluate comprising PMIDA is typicallyrecycled to the reaction system. As regeneration proceeds, the chloridecontent typically declines in the caustic regeneration solution exitingthe column. Advantageously, a portion of the caustic regenerationsolution, particularly that exiting the column toward the end of theregeneration cycle, may be preserved and used in a subsequentregeneration cycle in the same or a parallel PMIDA removal column.

Although an anion exchange resin which has a substantially higheraffinity for PMIDA than for glyphosate is preferably selected for column205, some glyphosate is typically removed along with PMIDA from themother liquor or other solution that is processed in the column. Theincidence of glyphosate removal may be relatively significant when thecolumn contains fresh or freshly regenerated resin. As PMIDA accumulatesin the column, the glyphosate fraction moves down (or in any eventtoward the column exit) in a manner similar to the operation of achromatographic column. In an alternative embodiment of the process, theeffluent from column 205 may be monitored not only for PMIDA but alsofor glyphosate. As the column becomes loaded with PMIDA, glyphosatebreaks through first. When the column is eluted, a glyphosate fractioncomes off first and may be segregated for recycle, e.g., to theevaporative crystallizer. Prior to elution, the column is washed forremoval of residual glyphosate caught in the interstitial spaces betweenthe resin beads. The glyphosate content of the wash solution may also besufficient to justify recycle to the evaporative crystallizer.

Where the operation of column 205 is monitored by use of device 207, thethreshold voltage at which a significant current density is realized mayfirst be observed to decline to a value reflective of the oxidation ofglyphosate. Such threshold voltage substantially prevails until PMIDAbreakthrough approaches. During elution, a similar voltage response orrequirement should be observed during elution of the glyphosate fractionwhich may be directed, e.g., to a feed tank for the evaporativecrystallizer. When the voltage required to sustain a target currentdensity declines to a value reflective of the oxidation of PMIDA, theeluate may be redirected for recycle to the reactor, or alternatively tothe purge.

According to a further alternative for recovery of glyphosate, a columnloaded with both glyphosate and PMIDA may be initially eluted with arelatively weak base such as isopropylamine (“IPA”) to remove therelatively weakly sorbed glyphosate in the form of the salt. Optionallyand preferably, neat liquid IPA can be used for the elution, whichproduces an eluate consisting of a relatively concentrated solution ofthe IPA salt of glyphosate. This eluate may directed to neutralizationand mixing tank 127 and used directly in producing aqueous IPAglyphosate concentrates.

In accordance with a further process alternative, as mentioned above,another column comprising an ion exchange zone comprising a resineffective for sorption of glyphosate, typically a further ion exchangecolumn, can be provided downstream of column 205. This column is notshown in FIG. 3 but may be positioned to receive the process stream thathas been passed in series through columns 203 and 205, or in seriesthrough columns 201, 203 and 205.

Finishing Reactor in Product Recovery Process

According to a further alternative, PMIDA can be removed from productrecovery process streams by catalytic oxidation to glyphosate. Inaddition to or in lieu of a finishing reactor as described above in theprincipal reaction train, polishing reactor(s) can be positioned in oneor more process streams within a product recovery system of the typeillustrated in FIG. 1. For example such a reactor could be positioned inthe feed stream to evaporative crystallizer 111 (as a pre-recoverypolishing reactor), in mother liquor stream 131 exiting evaporativecrystallizer centrifuge 121 (and/or 137), or elsewhere in the process.

Such further finishing reactor can optionally be operated with only acarbon catalyst. Moreover, since only marginal oxidation is involved,thermal effects are minimal, making it at least potentially advantageousto operate the reactor as a flow reactor with a fixed bed of catalyst,thus enhancing the driving force for substantial extinction of PMIDA.Where the reactor is placed in stream 131, ahead of the purge stream,the effect on overall yield of the marginal oxidation of glyphosate toAMPA is minimal. Oxidation reaction systems for preparation ofglyphosate reaction solutions by catalytic oxidation of a PMIDAsubstrate including finishing or pre-recovery polishing reactors aredescribed by Haupfear et al. in U.S. Application Publication No. U.S.2002/0068836 A1, the entire contents of which is incorporated herein byreference.

Crystallizer Operations

Process options effective to produce a product of relatively low PMIDAcontent have implications for the operation of evaporative crystallizer111. PMIDA has been found to function as a solubilizer for glyphosate.Thus, where the reaction system is operated under such conditions as toyield a filtered product reaction solution of relatively low PMIDAcontent, and/or where the filtered reaction solution is passed through afinishing reactor for further conversion of PMIDA to glyphosate, and/orwhere PMIDA is removed from recycle mother liquor by ion exchange,solubility of glyphosate in the recycle mother liquor can be lowered. Ata given system pressure, a lower PMIDA/glyphosate ratio causescrystallization to commence at relatively lower temperature, which canresult in fouling of process side heat exchanger surfaces in orassociated with the evaporative crystallizer.

FIG. 4 illustrates an evaporative crystallization system modified toaccommodate low PMIDA content in the feed solution without excessivefouling of the heat exchange surfaces. In the system of FIG. 4,crystallizer 109 comprises a vapor liquid separator 301, an externalheat exchanger 303, and an axial or centrifugal circulation pump 305 andline 307 for circulation of the crystallization slurry between the vaporliquid separator through the heat exchanger. A mist eliminator 309 inthe upper portion of the vapor liquid separator helps to collectentrained liquid and return it to the liquid phase within the separatorbody. Crystallization slurry is drawn off through port 311 in thecirculation line for delivery to centrifuge 121 and optionallycentrifuge 137. Fouling of heat exchanger 303 is potentiallyattributable to accumulation of glyphosate on the process side tubesurfaces, but may also be attributable to plugging of the heat exchangertubes with large chunks of crystalline material which may calve off thewalls of separator 301.

It may further be noted that the commencement of crystallization atlower temperature results in an enhanced crystallization yield. Whilethis effect may be advantageous from the standpoint of initialcrystallizer productivity, and marginally beneficial with regard toyield on raw materials, the higher solids content of the circulatingslurry is believed to have an adverse effect on heat transfer. Increasedsolids content increases the effective viscosity of the circulatingslurry, thereby increasing pressure drop through the heat exchanger. Ata given limiting pump head, this results in a decreased flow rate,decreased velocity along the process side of the tube wall, andconsequently decreased heat transfer coefficients. Thus, even withoutany fouling or plugging of tubes, heat transfer rates and productivitycan be compromised by the higher solids content obtained as thecrystallization temperature drops with PMIDA content.

In any event, injection of water into the circulating pump suctionimposes a sensible heat load that tends to reduce the rate ofprecipitation in the tubes. Although water injection does not reduce thesteady state composition of the liquid phase in the vapor/liquidseparator, it marginally reduces the degree of supersaturation in theliquid phase entering the heat exchanger, and may thus marginally reducethe tendency of the tubes to foul by further encrustation withglyphosate. Perhaps more significantly, it reduces the solids content ofthe slurry passing through the heat exchanger, thus reducing theviscosity, and contributing to increased process side velocity and heattransfer coefficients.

Injection of water above the mist eliminator is useful in minimizingpressure drop through the mist eliminator and controlling the extent ofcrystallization on the walls of the separator. Increasing the slurrycirculation rate via pump 303 serves to reduce the temperature rise inthe heat exchanger and enhance the scouring action of the circulatingslurry, further contributing to control of fouling.

Aside from the complications which it can create in the operation of theevaporative crystallizer, ion exchange also functions to reduce thechloride and phosphate content of the mother liquor circulating in theevaporative crystallization system. Whether as a result of lowerchloride and phosphate content or otherwise, it has been found thatenhanced crystal growth is achieved in the evaporative crystallizer inoperations wherein PMIDA, and necessarily also chloride and phosphate,is removed by ion exchange. The larger crystals thus produced havesuperior dewatering properties as compared to the crystals obtained inan evaporative crystallization system wherein a mother liquor ofrelatively high PMIDA, Cl⁻, and/or phosphate concentration circulatesbetween the evaporative crystallizer and centrifuge 121 or 121 and 137.Production of relatively larger crystals is advantageous in removal ofresidual impurities, including PMIDA, by separation of solids frommother liquor in the centrifuge(s) and washing of the centrifuge cake.It has further been observed that, where the crystallizer is operated toconsistently generate relatively large glyphosate particles, the foulingeffect of reduced PMIDA content is at least partially offset. Heatexchange surfaces are generally less prone to fouling in an operationwherein heat is transferred to a slurry comprising relatively largeparticles than in an operation where relatively fine crystals areproduced.

Programmed Control Scheme

The present invention contemplates the use of essentially allcombinations and permutations of the various measures that are describedhereinabove for reducing the PMIDA content of a glyphosate product. Insome instances, it may not be technically feasible or economicallyattractive to achieve a target PMIDA concentration by resort solely toincreased oxygen flow rate, solely to increased purge, or solely toanother single process stratagem outlined herein. Although certainprocess modifications such as ion exchange, where justified, may bequite sufficient to achieve any desired PMIDA level, there can still beadvantages in adopting ion exchange in combination with otheroperational variations.

In practicing the various methods of the invention, operationalstability, economic optimization, product and emission specificationand/or other advantages and constraints may be met or achieved by aprogrammed control scheme under which a combination of various measuressuch as increased oxygen flow, purge adjustment, allocation of PMIDAamong plural product forms, ion exchange conditions, process flows,reactor and crystallizer temperatures, reactor and crystallizerpressures, etc., may be monitored and controlled at values which achievea target PMIDA specification in one or more glyphosate product formsaccording to an optimal or otherwise desirable operational mode. Inaccordance with such a control scheme, signals conveying the currentvalues of various parameters and the control set points for the controlloops for such parameters may be transmitted to a programmed controllerwhich, in response to these inputs, may generate out put signals toadjust the various set points according to an algorithm inscribed incontroller software. For example, the algorithm may be adapted toachieve a target PMIDA content in a specified glyphosate product form atminimum cost, and/or at maximum throughput, and/or to meet other productspecifications, and/or to conform to emission standards, etc.

Such a program may be periodically adjusted as necessary to reflectchanges in raw material prices, product demand, production scheduling,environmental conditions, etc.

Glyphosate Product

By implementation of one or more of the process modifications andstratagems as described above, a manufactured glyphosate product may berecovered and removed from the process in a desired form with a PMIDAcontent of less than, 6,000 ppm, 5,000 ppm, 4,000 ppm, 3,000 ppm, 2,000ppm, 1,000 ppm, 600 ppm or even significantly lower. A glyphosateproduct of such low PMIDA level can be produced, for example, in theform of a solid crystalline glyphosate acid, or in the form of anaqueous concentrate of glyphosate salt, such as a potassium orisopropylamine salt having a glyphosate content of at least about 360gpl, a.e., preferably at least about 500 gpl, a.e., more preferably atleast about 600 gpl, a.e.

Glyphosate having a relatively low PMIDA content, e.g., not greater thanabout 0.45 wt. % acid equivalent on a glyphosate, a.e., basis, can beprepared by any of a variety of manufacturing processes. Significantcommercial advantages result from the preparation of glyphosate by aprocess comprising the catalytic oxidation of a PMIDA substrate asdescribed in detail hereinabove. Glyphosate obtained in this manner hasa very low glyphosine content, typically less than about 0.010 wt. %acid equivalent on a glyphosate a.e. basis. It generally has a small butacceptable glycine content, i.e., at least about 0.02 wt. % acidequivalent as also computed on a glyphosate, a.e., basis. PMIDA-derivedglyphosate product may also include small, but acceptable concentrationsof a number of other by-products and impurities. These may include forexample: iminodiacetic acid or salt thereof (IDA) in a concentration ofat least about 0.02 wt. % acid equivalent on a glyphosate, a.e., basis;N-methyl glyphosate or a salt thereof (NMG) in a concentration of atleast about 0.01 wt. % on a glyphosate, a.e., basis; N-formyl glyphosateor a salt thereof (NFG) in a concentration of at least about 0.010 wt. %acid equivalent on a glyphosate, a.e., basis;iminobis(methylenephosphonic acid) or a salt thereof(iminobis) in aconcentration of at least about 0.010 wt. % acid equivalent on aglyphosate, a.e., basis; and N-methylaminomethylphosphonic acid (MAMPA)or a salt thereof in a concentration of at least about 0.010 wt. % acidequivalent on a glyphosate, a.e., basis.

These relative proportions generally apply regardless of the form of theglyphosate product, i.e., regardless of whether it is in the form ofsolid state glyphosate acid or a concentrated aqueous liquid solutioncomprising a glyphosate salt such as, for example, a potassium,isopropylamine, monoammonium or diammonium salt. Preferred aqueousconcentrates comprise at least about 360 grams per liter glyphosate onan acid equivalent basis, with proportionate minor concentrations of thecommon by-products and impurities as listed above.

Further detailed limits and ranges for IDA, NMG, AMPA, NFG, iminobis,and MAMPA are set out below. All are expressed on an acid equivalentbasis relative to glyphosate, a.e.

More typically, the IDA content may be between about 0.02 wt. % andabout 1.5 wt. %, e.g., between about 0.05 wt. % and about 1.0 wt. %, ona glyphosate a.e. basis. Preferably, the IDA content is not greater thanabout 0.58 wt. %, not greater than about 0.55 wt. %, or not greater thanabout 0.50 wt. % on the same basis. In most operations, the productobtained has an IDA content between about 0.1 and about 0.58 wt. %,between about 0.1 and about 0.55 wt. %, between about 0.02 and about0.55 wt. %, or between about 0.1 and about 0.50 wt. %.

Generally, the NMG content is between about 0.02 and about 1.5 wt. %,for example, between about 0.02 and about 1.0 wt. %, or between about0.070 and about 1 wt. % on a glyphosate, a.e., basis. Preferably, theNMG content is not greater than about 0.55 wt. % or not greater thanabout 0.50 wt. %.

The glyphosate product also typically contains aminomethylphosphonicacid or a salt thereof (AMPA) in a concentration that may beincrementally higher than that of glyphosate products which haverelatively higher residual PMIDA content. For example, the AMPA contentmay range between about 0.15 and about 2 wt. %, more typically betweenabout 0.2 and about 1.5 wt. % aminomethylphosphonic acid or a saltthereof on a glyphosate, a.e., basis. In most instances, the AMPAcontent is at least about 0.30 wt. % on the same basis.

The NFG content is ordinarily between about 0.01 and about 1.5 wt. %,e.g., between about 0.03 and about 1.0 wt. %, more typically betweenabout 0.010 and about 0.70 wt. % on a glyphosate, a.e., basis. It isgenerally preferred that the NFG content be not greater than about 0.70wt. %, not greater than about 0.60 wt. %, not greater than about 0.50wt. %, not greater than about 0.40 wt. %, or not greater than about 0.30wt. % on the same basis.

Typically the iminobis content of the glyphosate product is betweenabout 0.1 and about 1.5 wt. %, e.g., between about 0.2 and about 1.0 wt.% on a glyphosate, a.e., basis. Preferably, the iminobis content is notgreater than about 0.8 wt. % iminobis(methylenephosphonic acid),normally between about 0.2 and about 0.8 wt. % on the same basis.

The MAMPA content is ordinarily between 0.1 about and about 2 wt. %,e.g., between 0.15 about and about 1.0 wt. % on a glyphosate, a.e.,basis. Most typically, the MAMPA content is at least about 0.25 wt. %MAMPA on the same basis. Most PMIDA-derived product comprises betweenabout 0.25 and about 0.6 wt. % MAMPA.

Although the typical levels of these various impurities and by-productsare inconsequential so far as the function, use and handling of theglyphosate product is concerned, they serve as markers which distinguisha product produced by catalytic oxidation of PMIDA from glyphosateproduct as produced by other processes. The presence of such impuritiesand by-products in the upper portions of the above described ranges havesome measurable impact on manufacturing process yields, and thus onproduct manufacturing cost.

Other Glyphosate Manufacturing Processes

Glyphosate product of low PMIDA content may also be manufactured byprocesses that use substrates such as AMPA or glycine. Each of theseprocesses generates a profile of by-products and impurities that issomewhat different from that of the PMIDA oxidation process. Forexample, the product of the glycine process most typically containsglyphosine in a concentration greater than about 0.010 wt. %, moretypically at least about 0.1 wt. %, and most typically in the range ofabout 0.3 to about 1 wt. %, all on a glyphosate, a.e., basis. Theproduct of the AMPA-based process may have a modest to significantfraction of unreacted AMPA, though the product of the PMIDA process canhave a comparable AMPA content, especially when latter is operated tominimize residual PMIDA and the former to minimize residual AMPA. Theglycine content of the AMPA process product is generally significantlylower than 0.02 wt. % on a glyphosate, a.e., basis.

According to an alternative embodiment of the present invention,glyphosate of low PMIDA content may be produced from glycine, e.g., by aprocess as described in U.S. Pat. No. 4,486,359, which is expresslyincorporated in its entirety herein by reference. In this process,glycine is initially reacted with paraformaldehyde in the presence oftriethylamine to produce N,N-bis(hydroxymethyl)glycine. The reaction isconducted in a methanol medium, typically at MeOH reflux temperature(i.e., about 65° C.). The N,N-bis(hydroxymethyl)glycine intermediate isreacted with dimethyl phosphite to yield an ester, which theabove-mentioned patent characterizes as the methyl ester of glyphosate.The ester is hydrolyzed in HCl to glyphosate acid. This productgenerally has a glyphosine content in excess of 0.010 wt. %, moretypically between about 0.05% and about 2% on a glyphosate, a.e., basis.Commercial sources of glycine process glyphosate may commonly containbetween about 0.2% and about 1.5% by weight glyphosine and between about0.05% and about 0.5% by weight glycine, more typically between about 0.3and about 1% by weight glyphosine and between about 0.1 and about 0.3%by weight glycine, all on a glyphosate, a.e., basis.

In an alternative to the process of U.S. Pat. No. 4,486,359, JapanesePublished Application Hei 9-227583 (application no. Hei-9-6881)describes a process in which the reaction between paraformaldehyde andglycine may be conducted in the presence of tributylamine rather thantriethylamine, and the ester intermediate may be hydrolyzed in analkaline medium such as NaOH rather than in acidic medium such as HCl.The Japanese patent publication reports that the base hydrolysis mayproduce a product of lower glyphosine content than the product of theprocess of U.S. Pat. No. 4,486,359.

In conducting the process, a source of formaldehyde, preferablyparaformaldehyde is mixed with a reaction medium comprising C₁ to C₄alcohol at moderately elevated temperature, tributylamine is added tothe resulting solution and the mixture preferably agitated at about 35°to 50° C. for typically 30 to 60 minutes. Glycine is added to thealcohol medium in a proportion which preferably assures a formaldehydeto glycine molar ratio from about 1 to 5, and the glycine is preferablycompletely dissolved in the medium. Preferably, the molar ratio oftributylamine to glycine is from about 0.5 to about 3. The temperatureis maintained at least about 30° C., preferably between about 50° andabout 60° C. for typically about 10 to 60 minutes, resulting in reactionof glycine with formaldehyde to form the tributylamine salt ofN-methylolglycine. A dialkylphosphite, e.g., dimethylphosphite, is thenadded to the solution under agitation at elevated temperature,preferably at least about 50° C., more typically about 65° to about 80°C., conveniently under alcohol reflux, preferably at a molar ratio toN-methylolglycine from about 0.6 to about 2.0. Dialkylphosphitecondenses with the tributylamine salt of N-methylolglycine to yield anester intermediate depicted in the Japanese patent publication as thedialkyl ester of the tributylamine carboxylate salt of glyphosate.Addition of a strong base such as NaOH, to this solution saponifies theester, liberates tributylamine and forms the Na salt of glyphosate. Thereaction mixture separates into two liquid phases, yielding an upperlayer containing tributylamine and a lower layer comprising a solutionof Na or K salt of glyphosate. Tributylamine may be recovered from theupper layer for recycle. The lower layer may be acidified to crystallizeglyphosate acid.

In accordance with the present invention, the alkaline hydrolysis may beconducted with a strong base comprising a desired countercation such as,e.g., KOH, as a step in the preparation of an aqueous concentrate of thepotassium salt of glyphosate. Where the phase separation is carried outunder conditions that assure substantially quantitative partition oftributylamine to the upper layer, the lower layer may be used directlyin the preparation of an aqueous glyphosate concentrate comprising thepotassium salt. Alternatively, the glyphosate salt may be acidified toprecipitate glyphosate acid, and the glyphosate acid separated byfiltration or centrifugation and washed, and the washed glyphosatewet-cake reslurried with water and base to produce the desired salt. Inthe latter process, the advantage of using KOH for the conversion ofintermediate ester to glyphosate salt is diminished. Where triethylamineis used as the alkylamine, it can be quantitatively removed bydistillation of the hydrolyzate, which may in certain instancesfacilitate direct preparation of a concentrate of the glyphosate salt ofthe base used for the conversion of the intermediate ester. Preferably,the concentrate comprises at least about 360 gpl glyphosate on an acidequivalent basis.

Regardless of whether the aqueous or solid glyphosate concentrate isprepared from glyphosate produced by oxidation of PMIDA or fromglyphosate produced from glycine or other starting material, theconcentrates of the invention include mixed countercation concentratescomprising any combination of monoammonium, diammonium, isopropylamine,potassium, dipotassium, sodium, monoethanolamine, ethylamine,ethylenediamine, n-propylamine, hexamethylenediamine, ortrimethylsulfonium salt. A preferred combination may comprise potassium,or a mixture of potassium and isopropylamine salts, wherein each ofpotassium and isopropylamine is in a mole ratio to glyphosate betweenabout 0.1 and about 0.9. In such a concentrate, the mole ratio ofisopropylamine to potassium may be between about 0.1 and about 0.9, incertain embodiments between about 0.2 and about 0.8, and in certainparticular embodiments between about 0.3 and about 0.7. In such mixedcountercation concentrates, the mole ratio of the sum of isopropylamineand potassium to glyphosate may typically be between about 0.7 and about1.2.

As far as is known, glyphosate has not been manufactured on a commercialscale in the United States using tributylamine and/or an alkalinehydrolysis process. However, it is understood that this process may becapable of producing a glyphosate product of the present invention,preferred embodiments of which contain relatively low concentrations ofglyphosine. For example, it is understood that the alkaline hydrolysisprocess may be conducted in a manner effective to yield a glyphosateproduct containing glyphosine in a proportion between about 0.05 toabout 0.8 wt. %, about 0.05 to about 0.6 wt. %, about 0.05 to about 0.5wt. % or about 0.05 to about 0.4 wt. %, about 0.1 to about 0.8 wt. %,about 0.1 to about 0.6 wt. %, 0.1 to 0.5 wt. %, 0.1 to 0.4 wt. % orabout 0.1 to 0.3 wt. %, basis glyphosate a.e. Such product may typicallycontain glycine in a concentration between about 0.05 and about 4 wt. %,more typically between about 0.05 and about 2 wt. %, or between about0.1 and about 0.5 wt. %, on a glyphosate, a.e., basis.

As noted above, aqueous liquid concentrates comprising agronomicallyacceptable salts of glyphosate preferably contain a surfactant thatpromotes penetration of the herbicide into the foliage of the plant.Cationic surfactants are generally preferred, but nonionic surfactantsand combinations of cationic and nonionic surfactants are alsoadvantageous. Particularly preferred cationic surfactants includealkoxylated alkylamines, alkoxylated etheramines, alkoxylated phosphateesters, and combinations thereof. It will be understood that the presentinvention encompasses each all of the various PMIDA-based, glycine-basedand other glyphosate products described or referred to above incombination with such surfactants or combinations of surfactants.

To provide a reliable commercial source of glyphosate having arelatively low residual PMIDA content, it is necessary to either operatethe manufacturing process on a sustained basis to consistently produceglyphosate product of low PMIDA content, or to segregate product fromdesignated operations in order to accumulate commercial quantities oflow PMIDA product.

Although glyphosate products having a low PMIDA content have beenincidentally produced on a transient basis during startup of amanufacturing facility for the catalytic oxidation of PMIDA toglyphosate, or in operation well below rated capacity, the processes ofthe prior art have not been effective for the preparation of a low PMIDAglyphosate product on a continuing basis during steady state operationsat or near capacity. Thus, each of the various glyphosate products ofthe invention encompasses a lot, run, shipment, segregate, campaign orsupply of glyphosate product as produced by a process capable ofmaintaining a low PMIDA content on a continuing basis. According to thepresent invention, such a lot, run, shipment, campaign, segregate orsupply comprises a quantity of solid state glyphosate acid, orconcentrated aqueous solution of glyphosate salt, comprising at least1500 metric tons, preferably at least about 3000 metric tons, glyphosateon a glyphosate a.e. basis.

For purposes of this invention, a “lot” may be considered a designatedquantity of glyphosate product that is produced under substantiallyconsistent process conditions in a particular manufacturing facilityduring a defined period of operations or over a designated period oftime. Production of the lot may be interrupted for production of otherglyphosate product or non-glyphosate product, or purge of impuritiesfrom the process, but not otherwise by catalyst replacement, turnaroundor startup operations. Glyphosate may be produced according to variousdifferent processes, some of which (e.g., a process comprising theaqueous phase catalytic oxidation of PMIDA) can be conducted in either abatch or continuous mode in the oxidation step and/or or in the recoveryof glyphosate by crystallization thereof from an aqueous medium. Withreference to a process comprising a batch reaction and/or batchglyphosate crystallization operation, it is understood that a lot maycomprise the product of a plurality of batches.

A “run” is quantity of glyphosate product made in a particularmanufacturing facility in continuing or consecutive operations over adesignated period without interruption for maintenance, catalystreplacement, or catalyst loading. It may include both startup and steadystate operations. With reference to a batch reaction and/or batchglyphosate crystallization operation, it is understood that a run maycomprise the product of a plurality of batches.

A “campaign” is a series of runs conducted over an identifiable periodof time during which the runs may be interrupted by other runs not partof the campaign or by purge of impurities, or for maintenance, but notby turnaround or catalyst replacement. No more than one of the runs mayinclude startup operations; provided, however, that more than one of theruns may comprise operation at a rate more than 30% below establishedcapacity. Compare the description of startup operations as set outhereinbelow.

A “shipment” is a commercial quantity of glyphosate product transportedto a particular customer or user in either a single unit, singlecombination of units, consecutive units, or consecutive combinations ofunits without interruption by transport of a commercial quantity of aglyphosate product of materially different average PMIDA content on aglyphosate, a.e., basis to the same user or customer. A materiallydifferent PMIDA content is PMIDA content that is either more than 0.15wt. % higher than the average PMIDA content of the shipment on aglyphosate, a.e., basis, more than 35% higher than the average PMIDAcontent of the shipment on a PMIDA basis, or is above 4500 ppm on aglyphosate a.e. basis.

A “supply” is a series of shipments that may be interrupted by othershipments of glyphosate product to other customers or users.

A “segregate” is a quantity of glyphosate product that is isolated fromother glyphosate product produced in the same manufacturing facilityover the same period of time (i.e., the time during which the segregateis produced). The segregate may be produced in different runs, and maybe allocated among different shipments or different supplies.

Startup operations are operations that are conducted in a manufacturingfacility in which glyphosate product has not previously been produced,or directly following interruption of the production of glyphosateproduct and removal of a substantial fraction of the inventory ofprocess liquids contained in process equipment, with the effect oflowering the total inventory of by-products and impurities in theprocess facility by at least 25 wt. %. Impurities and by-productsinclude PMIDA, IDA, AMPA, NMG, NFG, iminobis(methylenephosphonic acid),MAMPA, formic acid, NMIDA, glycine and glyphosine. For purposes of thisinvention, operations at a rate that is more than 30% below currentlyestablished capacity of a manufacturing facility is also deemed withinthe ambit of startup operations.

OTHER DEFINITIONS

Unless otherwise noted, terms and abbreviations are to be understoodaccording to conventional usage by those of ordinary skill in therelevant art. Definitions of common terms in molecular biology may alsobe found in Rieger et al., Glossary of Genetics: Classical andMolecular, 5th edition, Springer-Verlag: New York, 1991; and Lewin,Genes V, Oxford University Press: New York, 1994. The nomenclature forDNA bases as set forth at 37 CFR §1.822 is used.

“Affinity” as used herein means the tendency of an ion exchange resin tocomplex with another species, such as PMIDA or glyphosate, under theexisting process conditions, including the particular combination ofacids, solvents, and other ingredients that are present.

When a maximum or minimum “average number” is recited herein withreference to a structural feature such as oxyethylene units or glucosideunits, it will be understood by those skilled in the art that theinteger number of such units in individual molecules in a surfactantpreparation typically varies over a range that can include integernumbers greater than the maximum or smaller than the minimum “averagenumber”. The presence in a composition of individual surfactantmolecules having an integer number of such units outside the statedrange in “average number” does not remove the composition from the scopeof the present invention, so long as the “average number” is within thestated range and other requirements are met.

A transgenic “event” is produced by transformation of a plant cell withheterologous DNA, e.g., a nucleic acid construct that includes atransgene of interest; regeneration of a population of plants resultingfrom the insertion of the transgene into the genome of the plant cell,and selection of a particular plant characterized by insertion into aparticular genome location. The term “event” also refers to the originaltransformant plant and progeny of the transformant that include theheterologous DNA.

“Exogenous” refers to materials originating from outside of an organismor cell. This typically applies to nucleic acid molecules used inproducing transformed or transgenic host cells and plants.

“Fruiting branch” refers to a reproductive branch of a cotton plant uponwhich the fruit (boll) appears and typically arises at the fourththrough eighth plant node.

The term “gene” refers to chromosomal DNA, plasmid DNA, cDNA, syntheticDNA, or other DNA that encodes a peptide, polypeptide, protein, or RNAmolecule, and regions flanking the coding sequence involved in theregulation of expression.

“Glyphosate-tolerant” refers to a plant exhibiting reduced phytotoxiceffects from application of glyphosate (e.g., N-(phosphonomethyl)glycineor a salt thereof) on the plant.

Herbicidal effectiveness is one of the biological effects that can beenhanced through this invention. “Herbicidal effectiveness,” as usedherein, refers to any observable measure of control of plant growth,which can include one or more of the actions of (1) killing, (2)inhibiting growth, reproduction or proliferation, and (3) removing,destroying, or otherwise diminishing the occurrence and activity ofplants. The herbicidal effectiveness data set forth herein report“control” as a percentage following a standard procedure in the artwhich reflects a visual assessment of plant mortality and growthreduction by comparison with untreated plants, made by techniciansspecially trained to make and record such observations. In all cases, asingle technician makes all assessments of percent control within anyone experiment or trial. Such measurements are relied upon and regularlyreported by Monsanto Company in the course of its herbicide business.

“Heterologous DNA” refers to DNA from a source different than that ofthe recipient cell.

“Homologous DNA” refers to DNA from the same source as that of therecipient cell.

“Layby” refers to the growth point at which a final herbicide groundapplication is made that is designed to eliminate or suppress weedsuntil harvest.

“Node” refers to a point along the main cotton plant stem from whichvegetative and fruiting branches originate.

When used in the context of a surfactant or a glyphosate salt,“predominantly” means at least about 50%, preferably at least about 75%and more preferably at least about 90%.

A “recombinant” nucleic acid is made by an artificial combination of twootherwise separated segments of sequence, e.g., by chemical synthesis orby the manipulation of isolated segments of nucleic acids by geneticengineering techniques.

The term “recombinant DNA construct” or “recombinant vector” refers toany agent such as a plasmid, cosmid, virus, autonomously replicatingsequence, phage, or linear or circular single-stranded ordouble-stranded DNA or RNA nucleotide sequence, derived from any source,capable of genomic integration or autonomous replication, comprising aDNA molecule that one or more DNA sequences have been linked in afunctionally operative manner. Such recombinant DNA constructs orvectors are capable of introducing a 5′ regulatory sequence or promoterregion and a DNA sequence for a selected gene product into a cell insuch a manner that the DNA sequence is transcribed into a functionalmRNA that is translated and therefore expressed. Recombinant DNAconstructs or recombinant vectors may be constructed to be capable ofexpressing antisense RNAs, in order to inhibit translation of a specificRNA of interest.

“Regeneration” refers to the process of growing a plant from a plantcell (e.g., plant protoplast or explant).

“Transcription” refers to the process of producing an RNA copy from aDNA template.

“Transformation” refers to a process of introducing an exogenous nucleicacid sequence (e.g., a vector, recombinant nucleic acid molecule) into acell or protoplast that exogenous nucleic acid is incorporated into achromosome or is capable of autonomous replication.

“Transformed” or “transgenic” refers to a cell, tissue, organ, ororganism into that has been introduced a foreign nucleic acid, such as arecombinant vector. A “transgenic” or “transformed” cell or organismalso includes progeny of the cell or organism and progeny produced froma breeding program employing such a “transgenic” plant as a parent in across and exhibiting an altered phenotype resulting from the presence ofthe foreign nucleic acid.

The term “transgene” refers to any nucleic acid sequence nonnative to acell or organism transformed into said cell or organism. “Transgene”also encompasses the component parts of a native plant gene modified byinsertion of a nonnative nucleic acid sequence by directedrecombination.

“Vector” refers to a plasmid, cosmid, bacteriophage, or virus thatcarries foreign DNA into a host organism.

Following are Examples presented to illustrate the present invention andare not intended to limit the scope of this invention. The examples willpermit better understanding of the invention and perception of itsadvantages and certain variations of execution.

EXAMPLES

The following Examples are presented to illustrate the present inventionand are not intended to limit the scope of this invention. The exampleswill permit better understanding of the invention and perception of itsadvantages and certain variations of execution. All glyphosateconcentrations are on a glyphosate acid equivalent (a.e.) basis and allconcentrations are on a weight basis unless stated otherwise.

In the following Examples 1, M1-M4, AO1, H1, H2, D1, M9 and M10,greenhouse tests were conducted to evaluate the relative effectivenessof compositions in reducing PMIDA-induced necrosis in ROUNDUP READY FLEXcotton. Compositions for comparative purposes included the following:

-   -   Composition A: which consists of approximately 37.2% a.e. by        weight of glyphosate IPA salt in aqueous solution together with        approximately 11.7% surfactant. The surfactant was a blend of an        alkoxylated alkylamine and an alkoxylated phosphate ester. The        IPA salt of glyphosate was made from a technical grade        glyphosate having <100 ppm PMIDA (dry weight basis) resulting in        non-detectable levels of PMIDA level in the composition.    -   Composition B: which consists of approximately 39.6% a.e. by        weight of glyphosate potassium salt in aqueous solution together        with approximately 10% surfactant. The surfactant was a blend of        alkoxylated coco and tallow amines. The potassium salt of        glyphosate was made from a technical grade glyphosate having        <100 ppm PMIDA (dry weight basis) resulting in non-detectable        levels of PMIDA level in the composition.    -   Composition C: which contains approximately 37.2% a.e. by weight        of glyphosate IPA salt in aqueous solution together with        approximately 12% surfactant. The surfactant was a blend of an        alkoxylated alkylamine and an alkoxylated phosphate ester. The        composition contained 280 ppm PMIDA, equivalent to approximately        720 ppm PMIDA (dry weight basis) in the technical grade        glyphosate from which the composition was prepared.    -   Composition D: sold by Monsanto Company as ROUNDUP WEATHERMAX        and containing approximately 39.9% a.e. by weight of glyphosate        potassium salt in aqueous solution. The PMIDA concentration was        determined to be 1890 ppm, equivalent to approximately 4760 ppm        PMIDA (dry weight basis) in the technical grade glyphosate from        which the composition was prepared.    -   Composition E: which contains approximately 37.2% a.e. by weight        of glyphosate IPA salt in aqueous solution together with        approximately 11.7% surfactant. The surfactant was a blend of an        alkoxylated alkylamine and an alkoxylated phosphate ester. The        IPA salt of glyphosate was made from a technical grade        glyphosate having 1880 ppm PMIDA (dry weight basis) resulting a        PMIDA level in the composition of 730 ppm.    -   Composition F: sold by Monsanto Company as ROUNDUP WEATHERMAX        and containing approximately 39.4% a.e. by weight of glyphosate        potassium salt in aqueous solution. The PMIDA concentration was        determined to be 550 ppm, equivalent to approximately 1340 ppm        PMIDA (dry weight basis) in the technical grade glyphosate from        which the composition was prepared.    -   Composition G: was prepared by blending two samples of        commercial ROUNDUP WEATHERMAX sold by Monsanto Company        containing glyphosate potassium salt in aqueous solution. The        blend comprised approximately 56.4% of a sample containing        0.085% PMIDA and 43.6% of another sample containing 0.174%        PMIDA. The resulting blend contained 0.1238% PMIDA, equivalent        to approximately 0.300% PMIDA (dry weight basis) in the        technical grade glyphosate from which the samples were prepared.    -   Composition H: sold by Monsanto Company as ROUNDUP WEATHERMAX        and containing approximately 39.5% a.e. by weight of glyphosate        potassium salt in aqueous solution and 0.205% PMIDA, equivalent        to approximately 0.498% PMIDA (dry weight basis) in the        technical grade glyphosate from which the composition was        prepared.    -   Composition I: sold by Monsanto Company as ROUNDUP WEATHERMAX        and containing approximately 39.8% a.e. by weight of glyphosate        potassium salt in aqueous solution. The PMIDA concentration was        determined to be 1740 ppm, equivalent to approximately 4190 ppm        PMIDA (dry weight basis) in the technical grade glyphosate from        which the composition was prepared.

For greenhouse testing of the glyphosate concentrates, 30 mL spraysolutions were prepared as follows:

-   1. A stock solution was prepared for each concentrate sprayed by    adding 14.502 g of concentrate to 15.50 g de-ionized (DI) water.-   2. From the stock solution, the following dilutions were made to    prepare the actual spray solution (total volume of 30 mL).

Stock DI Water Rate Desired Solution (mL) (mL) 1X (1260 g/ha) 2.11 27.892X (2520 g/ha) 4.22 25.78 4X (5040 g/ha) 8.43 21.57Greenhouse Testing

The following greenhouse testing procedure provides a highlyreproducible assay for showing PMIDA-induced necrosis in ROUNDUP READYFLEX cotton and was used for evaluating compositions of the Examples todetermine their effectiveness in reducing the necrosis.

-   1. Two seeds of a ROUNDUP READY FLEX cotton variety were planted in    six inch round plastic pots containing a commercially available    potting mix (Redi-Earth), supplemented with fertilizer (Osmocote    14-14-14 slow release, 100 g/ft³).-   2. Pots were then placed in a greenhouse with the following    conditions: 33° C. day/21° C. night, variable relative humidity, and    14-hour day-length. Water was provided as needed through    sub-irrigation.-   3. Upon emergence plants were thinned to one per pot.-   4. Plants were grown for 21-25 days in order to achieve a minimum    growth stage of four true leaves (five-six leaves was preferred).-   5. Plants were then transferred to a growth chamber with the    following conditions: 27° C./60% relative humidity day, 15° C./80%    relative humidity night, and 14-hour day-length. Plants were    maintained in these conditions for forty-eight hours.-   6. Plants were removed from the growth chamber for an application of    glyphosate with a known level of PMIDA. Applications were made    utilizing a standard research track sprayer with a single spray    nozzle (flat fan even spray tip). The sprayer was calibrated to    deliver ninety-four liters of spray solution per hectare at a spray    pressure of 165 kPa. Glyphosate application rates varied depending    upon the objectives of the test, but typically were 1260, 2520 and    5040 g/ha which are, respectively, 1×, 2× and 4× of the highest    proposed field use rates on ROUNDUP READY FLEX cotton.-   7. When applications were complete the plants were returned to the    growth chamber for another forty-eight hour incubation under the    conditions listed in number 5 above.-   8. Plants were evaluated at this point, two days after treatment (2    DAT), with a visual assessment of percent necrosis (tissue death)    relative to an untreated check plant. Maximum injury was evident at    this time point.-   9. Resulting assessment data was statistically evaluated by least    significant difference (LSD). The LSD is a valid statistical test    procedure for evaluating multiple comparisons. The magnitude of the    LSD value is related to the variability across replicates for each    comparison. The greater the variability among replicates the higher    the LSD value. Comparisons are thus made between mean values    generated across replicates. The LSD, typically provided as a 95%    confidence limit (LSD 0.05), specifies the minimum degree of    difference between mean comparisons that would be considered    statistically significant. In other words one is 95% sure that this    minimum difference is statistically valid. For example, where    Treatment A mean value is 10, Treatment B mean value is 15, and    Treatment C mean value is 20. Calculated LSD (0.05) is 7.2. The    difference between Treatment A and Treatment C would be considered    statistically significant, whereas Treatment B would not be    considered statistically different from either Treatment A or    Treatment C.

Example 1

Aqueous concentrate compositions were prepared containing PMIDA at knownconcentrations. For composition A-1, 0.05 g of dry PMIDA (99% assay)were added to 100 g of composition A and stirred until the PMIDA wasdissolved. PMIDA concentrations reported in these Examples weredetermined or confirmed by high-pressure liquid chromatography (HPLC)analysis in accordance with the procedure in Example 3 below.Compositions A-2 and A-3 were prepared in like manner using 0.15 g and0.20 g PMIDA, respectively.

TABLE 1a PMIDA g/ha % necrosis (2 DAT) Composition (1X, 2X, 4X rates)1260 g/ha 2520 g/ha 5040 g/ha A nd, nd, nd* 0 0 4 C 0.95, 1.90, 3.79 0 015 A-1 1.69, 3.39, 6.77 0 6 65 E 2.47, 4.95, 9.89 0 25 66 A-2 5.08,10.16, 20.3 4 40 83 D 5.97, 11.9, 23.9 9 51 79 A-3 6.77, 13.6, 27.1 9 6183 LSD (0.05) 4.4 9.2 8.8 *nd = not detected

Results show a clear titration effect as increasing levels of PMIDAcause a proportionate rise in necrosis. Maximum necrosis appears toreach a plateau at the 80-85% range as noted with the highestapplication rate and higher levels of PMIDA.

Example M1

Spray solutions for glyphosate application rates of 2520 and 5040 g/hawere prepared using composition D. All metal salts were tank-mixed at aglyphosate:metal salt weight ratio of 10:1. For each spray solution, theamount of metal salt required to give the 10:1 ratio was dissolved in anequal amount of water. This 50% w/w metal salt solution was then mixedwith the requisite amount of composition D and water to provide thedesired volume of spray solution. This resulted in Metal:PMIDA molarratios as follows:

Metal Salt CAS Number Metal:PMIDA Molar Ratio Ferric chloride 7705-08-029.6:1 Nickel sulfate 10101-97-0 18.2:1 hexahydrate Aluminum chloride7784-13-6 19.9:1 hexahydrate Cupric Nitrate (2.1) 19004-19-4 20.6:1hydrate Zinc sulfate 7446-20-0 16.7:1 heptahydrate Magnesium sulfate10034-99-8 19.5:1 heptahydrate Calcium chloride 10043-52-4 43.2:1(anhydrous)

TABLE M1a Necrosis Reduction % necrosis (2 DAT) Relative to ControlGlyphosate (g/ha) 2520 5040 2520 5040 PMIDA (g/ha) 11.9 23.9 11.9 23.9Tank-mix Additive None 38 78 na* na Ferric chloride 0 2 100% 97% Nickelsulfate 4 28 89% 64% Aluminum chloride 2 23 95% 71% Cupric Nitrate 3 2592% 68% Zinc sulfate 10 54 74% 31% Magnesium sulfate 46 73 0% 6% Calciumchloride 26 73 32% 6% LSD (0.05) 6.2 8 *na = not applicable

Several of the metal salts significantly reduce necrosis at bothapplication rates. These included nickel, zinc, aluminum, copper, andiron. Calcium and magnesium, known glyphosate antagonists, hadrelatively little impact on the degree of necrosis.

Example M2

An aqueous concentrate composition containing Iron(III) Citrate at knownIron:PMIDA molar ratios was prepared from composition F as follows:

Iron:PMIDA Composition F Iron (III) Citrate Molar Ratio (g) (g) 1.5:199.882 0.118 2.5:1 99.804 0.196 3.5:1 99.725 0.275

Composition D containing 1890 ppm PMIDA and no iron was used as acontrol.

TABLE M2a Necrosis Reduction % necrosis (2 DAT) Relative to ControlGlyphosate (g/ha) 1260 2520 5040 1260 2520 5040 Iron:PMIDA PMIDA (g/ha)(molar ratio) 1.76 3.52 7.04 1.76 3.52 7.04 No Iron 9 34 71 na na na1.5:1 0 2 16 100% 94% 77% 2.5:1 0 0 11 100% 100%  85% 3.5:1 0 1 9 100%97% 87% LSD (0.05) 1.6 3.4 7.5

Previous studies have shown that a formulation with PMIDA at 549 ppmwill produce necrosis of 60-65% at the high application rate.

An aqueous concentrate composition containing Iron(III) Citrate at knownIron:PMIDA molar ratios was prepared from composition G as follows:

Iron:PMIDA Composition G Iron (III) Citrate Molar Ratio (g) (g) 1.5:199.735 0.265 2.5:1 99.559 0.441 3.5:1 99.484 0.616

Composition D containing 1890 ppm PMIDA and no iron was used as acontrol.

TABLE M2b Necrosis Reduction % necrosis (2 DAT) Relative to ControlGlyphosate (g/ha) 1260 2520 5040 1260 2520 5040 PMIDA (g/ha) Ironcitrate:PMIDA 3.95 7.90 15.8 3.95 7.90 15.8 No Iron 9 34 71 na na na1.5:1 0 3 30 100% 91% 58% 2.5:1 0 1 18 100% 97% 75% 3.5:1 0 1 11 100%97% 85% LSD (0.05) 1.6 3.4 7.5

Previous studies have shown that a formulation with PMIDA at 1238 ppmwill produce necrosis at slightly lower levels than that of compositionD at all three application rates.

An aqueous concentrate composition containing Iron(III) Citrate at knownIron:PMIDA molar ratios was prepared from composition H as follows:

Iron:PMIDA Composition H Iron(III) Citrate Molar Ratio (g) (g) 1.5:199.562 0.438 2.5:1 99.272 0.728 3.5:1 98.984 1.016

Composition D containing 1890 ppm PMIDA and no iron was used as acontrol.

TABLE M2c Necrosis Reduction % necrosis (2 DAT) Relative to ControlGlyphosate (g/ha) 1260 2520 5040 1260 2520 5040 PMIDA (g/ha) Ironcitrate:PMIDA 6.54 13.08 26.16 6.54 13.08 26.16 No Iron 9 34 71 na na na1.5:1 0 18 43 100% 47% 39% 2.5:1 0 2 31 100% 94% 56% 3.5:1 0 0 30 100%100%  58% LSD (0.05) 1.6 3.4 7.5

Previous experience has shown that the composition with 2050 PMIDA willcause slightly more necrosis than composition D with 1890 ppm PMIDA.

Example M3

An aqueous concentrate composition containing iron(III) citrate in a2.5:1 molar ratio with PMIDA was prepared by mixing together 99.559 g ofcomposition G and 0.441 g iron(III) citrate.

An aqueous concentrate composition containing iron(III) sulfate pluscitric acid having an iron:PMIDA molar ratio of 2.5:1 was prepared byfirst dissolving 15.638 g iron(III) sulfate pentahydrate (CAS Number15244-10-7) into 46.48 g of a 50% aqueous solution of citric acid tomake an “iron sulfate+citric acid” premix. Then 1.381 g of the premixwas added drop-wise to 98.619 g composition G while stirringcontinuously.

An aqueous concentrate composition containing iron(III)ethylenediaminetetraacetic acid having an iron:PMIDA molar ratio of2.5:1 was prepared by mixing together 99.434 g of composition G and0.566 g iron(III) EDTA sodium salt hydrate (CAS Number 15708-41-5).

TABLE M3a Necrosis Reduction % necrosis (2 DAT) Relative to ControlGlyphosate (g/ha) 1260 2520 5040 1260 2520 5040 PMIDA (g/ha) IronAddition 3.95 7.90 15.8 3.95 7.90 15.8 None 9 34 71 na na na Ironcitrate 0 1 18 100% 97% 75% Iron sulfate + citric 0 2 20 100% 94% 72%acid Iron + EDTA 0 11 39 100% 68% 45% LSD (0.05) 1.6 3.4 7.5

There was no significant difference between iron citrate and ironsulfate plus citric acid relative to the reduction in necrosis at anyapplication rate. Iron plus EDTA was significantly less effective.

Example M4

The metal salt compositions in this Example were prepared as in ExampleM3 except that the metal salts were added to composition I which has1740 ppm PMIDA. Mixtures were prepared containing 1.5:1, 2.5:1 or 3.5:1Metal:PMIDA molar ratios.

TABLE M4a Necrosis Reduction % necrosis (2DAT) Relative to ControlGlyphosate (g/ha) 1260 2520 5040 1260 2520 5040 PMIDA (g/ha) MetalAddition metal:PMIDA 5.51 11.0 22.0 5.51 11.0 22.0 None 6 43 63 na na Nazinc sulfate + citric acid 1.5:1 2 40 67 67% 7% 0% zinc sulfate + citricacid 2.5:1 1 28 67 83% 35% 0% zinc sulfate + citric acid 3.5:1 4 23 6033% 47% 5% zinc oxide + citric acid 1.5:1 9 47 63 0% 0% 0 zinc oxide +citric acid 2.5:1 3 43 72 50% 0% 0% zinc oxide + citric acid 3.5:1 1 3857 83% 12% 10% Ferric sulfate + citric acid 1.5:1 0 20 57 100% 53% 10%ferric sulfate + citric acid 1.5:1 blended with zinc oxide + citric acid2.5:1 0 8 60 100% 81% 5% LSD (0.05) 3.1 9.2 10.4

Ferric sulfate plus citric acid was significantly more effective inreducing necrosis than either zinc sulfate plus citric acid or zincoxide plus citric acid. Ferric sulfate plus citric acid and zinc sulfateplus citric acid combined in the same formulation showed a significantlygreater degree of necrosis reduction at the 2520 g/ha glyphosateapplication rate than ferric sulfate plus citric acid alone.

Example AO1

Spray solutions for glyphosate application rates of 2520 and 5040 g/hawere prepared using composition D. All antioxidants were tank-mixed at aglyphosate:antioxidant weight ratio of 10:1. This resulted in anantioxidant:PMIDA weight ratio of 22:1. The sodium sulfite andL-ascorbic acid were added to the spray solutions as solids. Butylatedhydroxy anisole and butylated hydroxyl toluene were added as 33%solutions in 2-ethyl-1-hexanol. The hydroquinone was added as a 33%solution in ethanol and the resorcinol was added as a 50% aqueoussolution.

TABLE AO1a Necrosis Reduction % necrosis (2 DAT) Relative to ControlGlyphosate (g/ha) 2520 5040 2520 5040 PMIDA (g/ha) 11.9 23.9 11.9 23.9Tank-mix Additive None 49 78 na na butylated hydroxy anisole 10 55 80%29% butylated hydroxy toluene 10 60 80% 23% Hydroquinone 15 74 69%  5%Resorcinol 14 61 71% 22% L-ascorbic acid 33 78 33%  0% Sodium sulfite 3083 39%  0% LSD (0.05) 6.1 7.8

All antioxidants significantly reduced necrosis at the 2520 g a.e./haapplication rate. Butylated hydroxy anisole, butylated hydroxy toluene,and resorcinol also significantly reduced necrosis at the higherapplication rate.

Example H1

Spray solutions for glyphosate application rates of 2520 and 5040 g/hawere prepared using composition D. Additionally, urea (50% w/w solution)or glycerin were added to the spray solution on a % volume/volume (v/v)basis.

TABLE H1a Necrosis Reduction % Necrosis (2 DAT) Relative to ControlGlyphosate (g/ha) 2520 5040 2520 5040 PMIDA (g/ha) 11.9 23.9 11.9 23.9Tank-mix Additive Study 1 None 33 76 na na glycerin 2% v/v 29 65 12% 14%glycerin 4% v/v 18 45 45% 41% LSD (0.05) 6.4 9.5 Study 2 None 28 86 nana glycerin 4% v/v 5 70 82% 19% urea 8% v/v 18 75 36% 13% LSD (0.05) 77.8

Glycerin (4% v/v) and urea (8% v/v) significantly reduced necrosis inROUNDUP READY FLEX cotton.

Example H2

Various proprietary additives were used in the compositions of thisExample. They may be identified as follows:

Trade Name Chemical Description Surfynol 104Atetramethyl-6-decyne-4,7-diol Surfonic ADA-170 ethylenediamineethoxylate Tetronic 304 ethylenediamine ethoxylate/propoxylate PluronicL64 EO/PO block copolymer Agrimul PG 2069 decyl polyglucose

Spray solutions for glyphosate application rates of 2520 and 5040 g/hawere prepared using composition D. All tank-mix additives were tested ata glyphosate:additive weight ratio of 10:1. Tank-mix additives wereadded to the spray solution in neat form except for the following:

Tank-mix Additive Form Added to Spray Solution Polyethylene glycol 90050% aqueous solution Surfynol 104A 50% solution in ethyl hexyl alcoholAgrimul PG 2069 50% aqueous solution Corn syrup (light) 50% aqueoussolution trimethylol-propane 50% aqueous solution

TABLE H2a Necrosis Reduction % Necrosis (2 DAT) Relative to ControlGlyphosate (g/ha) 2520 5040 2520 5040 PMIDA (g/ha) 11.9 23.9 11.9 23.9Tank-mix Additive None 46 79 na na propylene glycol 49 81  0% 0%dipropylene glycol 45 80  2% 0% Ethylene glycol 40 78 13% 1% Diethyleneglycol 28 73 39% 8% triethylene glycol 40 75 13% 5% polyethylene glycol200 35 71 24% 10%  polyethylene glycol 900 31 75 33% 5%2-methyl-2,4-pentanediol 34 73 26% 8% 1,4-butanediol 28 73 39% 8%3-hexyne-2,5-diol 33 80 28% 0% Surfynol 104A 23 73 50% 8% SurfonicADA-170 33 73 28% 8% Tetronic 304 45 80  2% 0% Triethanolamine 34 76 26%4% Triisopropanolamine 49 84  0% 0% Pluronic L64 50 76  0% 4% Agrimul PG2069 36 80 22% 0% Glycerol propoxylate, 38 78 17% 1% mw 260 (1PO/OH)Corn syrup (light) 55 86  0% 0% trimethylol-propane 53 84  0% 0% LSD(0.05) 8.8 6.6

Several of these additives significantly decreased necrosis at the 2520g/ha application rate. These included diethylene glycol, polyethyleneglycol 200, polyethylene glycol 900, 2-methyl-2,4-pentanediol,1,4-butanediol, 3-hexyne-2,5-diol, Surfynol 104A, Surfonic ADA-170,triethanolamine, and Agrimul PG 2069.

Example D1

Spray solutions for glyphosate application rates of 2520 and 5040 g/hawere prepared using composition D. Dyes were tested at a glyphosate:dyeweight ratio of 10:1, 100:1 or 1000:1. The dyes were added to the spraysolution as aqueous solutions with the following concentrations: FD&CYellow #5 and FD&C Blue #1 were at 15% while the remaining dyes were at10%.

TABLE D1a Necrosis Reduction % necrosis Relative (2 DAT) to ControlGlyphosate (g/ha) 2520 5040 2520 5040 PMIDA (g/ha) Tank-mix Additiveglyphosate:dye 11.9 23.9 11.9 23.9 Study 1 None 49 78 na na FD&C Yellow#5  10:1 2 35 96% 55% LSD (0.05) 6.1 7.8 Study 2 None 38 78 na na FD&CYellow #5  10:1 6 38 84% 51% FD&C Yellow #5 100:1 31 55 18% 29% FD&CYellow #5 1000:1  28 69 26% 12% FD&C Blue #1  10:1 13 46 66% 41% LSD(0.05) 6.2 8 Study 3 None 54 73 na na FD&C Red #40 100:1 48 75 11% 0%FD&C Red #33 100:1 51 75 6% 0% FD&C Violet #1 100:1 34 75 37% 0% FastGreen FCF 100:1 53 78 2% 0% Methylene Blue 100:1 28 54 48% 26% LSD(0.05) 11.6 13.2

Results indicate that dyes in the spray solution that absorb light inthe visible light spectrum can decrease necrosis induced by PMIDA.

Example M5

A potassium glyphosate formulation containing iron (III) citrate tomitigate the adverse effects of PMIDA is prepared by simply mixing thefollowing ingredients in a 250 ml beaker. The mixture becomeshomogeneous in a few minutes at 23° C.

Weight Added Ingredient (grams) Description Potassium Glyphosate 84.258% K salt of glyphosate acid in Salt Concentrate water, containing47.387% a.e. glyphosate, 0.1974% PMIDA Blend of alkoxylated 10.0Proprietary Blend coco and tallow amines Agnique DFM 111S 0.0075 Asilicone defoamer from Cognis Corporation, Cincinnati, Ohio Iron (III)Citrate 0.713 (CAS Number 3522-50-7, containing 17.2% iron) fromSigma-Aldrich, St. Louis, Missouri De-ionized Water 5.078 Total weight100.00

The finished formulation contains 39.9% a.e. glyphosate, 0.1663% PMIDA,and 0.1226% iron, which is a 3 to 1 mole ratio of iron to PMIDA.

These values are calculated from the amounts and assays of theingredients.

-   -   0.842*47.387% a.e.=39.9% a.e. glyphosate in formulation    -   0.842*0.1974% PMIDA=0.1663% PMIDA in formulation    -   (0.713 g iron citrate/100 g)*(17.2% iron in iron        citrate)=0.1226% iron in formulation    -   0.1663 g/(226.97 g/mole of PMIDA)=0.7327×10⁻³ moles PMIDA    -   0.1226 g/(55.847 g/mole of iron)=2.195×10⁻³ moles iron

-   The mole ratio of Iron to PMIDA=(2.195/0.7327)=3.0.

Example M6

A potassium glyphosate formulation that uses a mixture of iron sulfatepentahydrate, zinc oxide, and citric acid to mitigate the effects ofPMIDA is prepared by mixing the ingredients given in the following tablein a 250 ml beaker. Before proceeding, the salts are premixed withcitric acid. A 50% citric acid solution is made by mixing 100 g ofcitric acid (CAS Number 77-92-9, anhydrous) with 100 g of de-ionizedwater. Adding 25.17 g of iron (III) sulfate pentahydrate (CAS Number15244-10-7, containing 21.6% iron) to 74.83 g of the 50% citric acidsolution yields the iron sulfate+citric acid premix. Adding 10.046 gzinc oxide (CAS Number 1314-13-2, containing 80.35% zinc) to 89.954 g ofthe 50% citric acid solution, and stirring until the oxide dissolves,produces the zinc premix. The components can now be mixed in a 250 mlbeaker with stirring.

Weight Added Ingredient (grams) Description Potassium Glyphosate 84.258% K salt of glyphosate acid in Salt Concentrate water, containing47.387% a.e. glyphosate, 0.1974% PMIDA Etheramine surfactant 7.48Proprietary Surfactant Agnique DFM 111S 0.01 A silicone defoamer fromCognis Corporation, Cincinnati, Ohio Sethness P212 0.01 Caramel dye fromSethness-Roquette Company, Chicago IL Premix of 1.128 Amounts bycomponent: Iron (III) Sulfate Added 0.284 g iron sulfate hydrate CitricAcid drop-wise 0.422 g citric acid Water 0.422 g water Premix of 1.431Amounts by component: Zinc Oxide Added 0.149 g zinc oxide Citric aciddrop-wise 0.641 citric acid Water 0.641 water De-ionized Water 5.741Total weight 100.00

The preparation used the same potassium glyphosate salt concentrate asExample M5, so the finished formulation contains 39.9% a.e. glyphosateand 0.1663% PMIDA. The iron content is 0.06134%, and the zinc content is0.1197%.

These values are obtained from the salt amount and metal assays of same.

-   -   0.284 g iron sulfate/100 g*21.6% iron in salt=0.06134% iron    -   0.149 g zinc oxide/100 g*80.35% zinc in oxide=0.1197% zinc    -   Moles of iron/100 g=0.06134 g/(55.847 g/mole)=1.098×10⁻³ moles    -   Moles of zinc/100 g=0.1197 g/(65.38 g/mole)=1.831×10⁻³ moles

-   The moles of PMIDA is the same as in Example M5, 0.7327×10⁻³ moles    PMIDA.

-   The mole ratio of iron to PMIDA (1.098/0.7327) is 1.5.

-   The mole ratio of zinc to PMIDA (1.831/0.7327) is 2.5.

Example M7

The metal salts to be tested were first dissolved in water at a highconcentration. This facilitates the handling and dilution required tomake the spray solutions. For example 15.0 grams of aluminum chloridehexahydrate (CAS Number 7784-13-6, containing 11.17% Al) was firstdissolved in 15 grams water to give a 50% solution in salt. To preparethe application mixture for the 2520 g (glyphosate acid)/ha, wherein themetal salt is to be applied 10 parts glyphosate acid to 1 part metalsalt, one needs to use 252.0 g/ha aluminum chloride hexahydrate. Thespray volume of water is usually 94 liters/ha. A simple ratio is used toscale the batch size to the amount needed for a small greenhouseapplication of 0.03 liters. Using composition 270 as the source ofglyphosate, containing 0.1890% PMIDA and 39.7% a.e. glyphosate, for theselected rate, (2520 g a.e./ha)/(94 l/ha)=“g needed”/0.03l) is solvedfor “g needed”, and one obtains 0.80425 g of glyphosate acid. Dividingby the glyphosate assay of composition 270, 0.80425 g a.e./(0.397 ga.e./g of composition=) one determines that 2.026 g of composition 270must be added to 0.03 liters. The “grams needed” calculation is repeatedfor the 252.0 g/ha rate for the metal salt, and after dividing by the50% assay of the premix, one determines that 0.1609 g of the 50% aqueousaluminum chloride hexahydrate premix must be added to the 0.03 liters.This completes the preparation of the spray solution, and the othermaterials are handled similarly.

Example M8

An isopropyl amine (IPA) glyphosate formulation with a metal salt addedto mitigate the effects of PMIDA is prepared by mixing the followingingredients in a 250 ml beaker equipped with a stirrer. Beforeproceeding, in a separate beaker, 100 grams of an “aluminum and citricacid” premix is made; 16.338 g of citric acid (CAS Number 77-92-9) isdissolved in 49.172 g of de-ionized water, then, while stirring, 34.44 gof aluminum (III) sulfate octadecahydrate (CAS Number 7784-31-8,containing 8.1% aluminum) is added. Continue stirring until the aluminumsalt dissolves completely. Once completed, the formulation can beprepared by adding the following.

Weight Added Ingredient (grams) Description Isopropyl amine 66.13 62%IPA salt of glyphosate acid in Glyphosate Salt water, containingConcentrate 45.93% a.e. glyphosate, 0.09569% PMIDA Ethoxylated tallow8.0 Proprietary Surfactant amine Premix of 0.810 Amounts by component:Al Sulfate 18Hydrate Added 0.279 g Al sulfate 18hydrate Citric Aciddrop-wise 0.133 g Citric acid Water 0.398 g Water De-ionized Water 25.06Total weight 100.00

The finished formulation contains 41% IPA salt of glyphosate, 30.37%a.e. glyphosate, 0.06346% PMIDA, 0.02260% aluminum, and an aluminum toPMIDA mole ratio of 3.

These values were calculated from the amounts and assays of theingredients.

-   -   66.13 g/100 g*62% IPA salt=41.00% IPA salt of glyphosate in        formulation    -   66.13 g/100 g*45.93% a.e. glyphosate=30.37% a.e. glyphosate in        formulation    -   66.13 g/100 g*0.09596% PMIDA=0.06346% PMIDA in formulation    -   0.279 g/100 g*8.1% Al in salt=0.02260% aluminum in formulation    -   Moles of PMIDA in formulation (0.06346 g/226.97 g/mole) are        0.2796×10⁻³ moles.    -   Moles of aluminum in formulation (0.02260 g/26.98 g/mole) are        0.8377×10⁻³ moles.

Example M9

Two spray solution sets (A and B) for glyphosate application to ROUNDUPREADY FLEX COTTON were prepared from ROUNDUP WEATHERMAX (MonsantoCompany), an aqueous glyphosate potassium salt concentrate. Theconcentrate used to prepare spray solution set A contained 0.2% PMIDAand the concentrate used to prepare a spray solution set B contained0.4% PMIDA. For each spray set, six spray solutions were prepared thatvaried with respect to the amount of added ferric sulfate content.Solution 1 of each spray set was prepared with no ferric sulfateaddition and solutions 2 through 6 of each set were prepared with ferricsulfate additions at a molar ratio of metal ion to PMIDA of 0.2:1,0.4:1, 0.6:1, 0.8:1 and 1:1, respectively. Using the greenhouse testingprotocol described above and an application volume of 94 L/hectare,spray solution set A was applied to ROUNDUP READY FLEX cotton atapplication rates of 1260, 2520 and 5040 grams acid equivalent perhectare and spray solution set B was applied at application rates of2520 and 5040 grams acid equivalent per hectare.

The results for the evaluation of the two spray solution sets arepresented in the following two tables.

% Necrosis 2 DAT for ROUNDUP WEATHERMAX Containing 0.2% by Weight PMIDAand Ferric Sulfate

% necrosis (2 DAT) Iron:PMIDA Spray Molar 1260 g 2520 g 5040 g SolutionRatio a.e./ha a.e./ha a.e./ha 1A 0 2 9 44 2A 0.2:1 0 4 34 3A 0.4:1 0 438 4A 0.6:1 0 2 19 5A 0.8:1 0 0 19 6A 1.0:1 0 1 24 LSD 0.4 7.2 10.8% Necrosis 2 DAT for ROUNDUP WEATHERMAX Containing 0.4% by Weight PMIDAand Ferric Sulfate

% necrosis (2 DAT) Iron:PMIDA Spray Solution Molar Ratio 2520 g a.e./ha5040 g a.e./ha 1B 0 28 66 2B 0.2:1 14 47 3B 0.4:1 11 49 4B 0.6:1 11 455B 0.8:1 3 38 6B 1.0:1 3 31 LSD 7.2 10.8

Iron to PMIDA ratios of 0.6:1 and higher significantly reduced necrosisat the two highest application rates with ROUNDUP WEATHERMAX containing0.2% PMIDA. When the PMIDA level was raised to 0.4%, all iron to PMIDAratios, including the lowest at 0.2:1, significantly reduced necrosis atboth 2520 and 5040 g glyphosate a.e./ha application rates. This may bedue to the greater magnitude of necrosis with 0.4% PMIDA allowing for amore clearly discernable decrease in necrosis with iron addition. Itshould be noted with the higher PMIDA levels that 0.8:1 and 1:1 ratioswere the only ones to reduce necrosis below the commercially acceptablelevel of about 5% at the 2× normal application rate (2520 g/ha). The 1:1ratio also reduced necrosis to a significantly greater degree thanratios of 0.2:1, 0.4:1, and 0.6:1 at the highest application rate. Thiswould suggest that as PMIDA levels increase and necrosis potentialincreases, the iron to PMIDA ratio may need to increase to mitigatecotton necrosis, and certainly within the context of ratios of 1:1 andlower.

Example M10

A comparison was made between the standard greenhouse incubationconditions of 27° C./60% relative humidity day, 15° C./80% relativehumidity night, 14 hour day, 48 hours before and after glyphosateapplication (as described in the greenhouse testing protocol and termed“low temp” conditions) versus higher temperature/higher humidityincubation conditions of 35° C./80% relative humidity day, 27° C./80%relative humidity night, 14 hour day, 48 hours before and afterglyphosate application (termed “high temp” conditions).

Two spray solutions for glyphosate application to ROUNDUP READY FLEXCOTTON were prepared from ROUNDUP WEATHERMAX (Monsanto Company)containing either 0.2% PMIDA or 0.4% PMIDA and without ferric sulfateaddition. Using an application volume of 94 L/hectare, each spraysolution was applied to ROUNDUP READY FLEX cotton at application ratesof 1260, 2520 and 5040 grams acid equivalent per hectare. The greenhousetesting protocol described above was utilized with either the “low temp”incubation conditions or the “high temp” incubation conditions. Theresults are reported in the table below.

% Necrosis 2 DAT for ROUNDUP WEATHERMAX Containing 0.2% and 0.4% byWeight PMIDA

% necrosis (2 DAT) 1260 g 2520 g 5040 g a.e./ha a.e./ha a.e./ha 0.2%PMIDA - low 1 9 44 temp 0.2% PMIDA - high 0 1 8 temp 0.4% PMIDA - low 028 65 temp 0.4% PMIDA - high 0 0 8 temp LSD 0.4 7.2 10.8

The data show that high temperature, high humidity incubation conditionsresult in less PMIDA-induced necrosis than do comparable treatmentsevaluated under “low temp” incubation conditions.

Example 2 Field Trials

Field trials were conducted at Fredricksburg, Tex., Leland, Miss., andLoxley, Ala., USA. Glyphosate formulations were applied to ROUNDUP READYFLEX cotton at the 5-6 leaf node stage of development or later and wasdependent upon environmental conditions to maximize necrosis expression.Application rates were 1250, 1680, and 2520 g glyphosate a.e./ha,representing 1×, 1.5×, and 2× rates. All treatments were replicated fourtimes in each study. Cotton necrosis was evaluated 2 DAT. Eight trialswere conducted for each example.

Commercial glyphosate formulations containing known amounts of PMIDAwere fortified as necessary with PMIDA and iron to give the compositionslisted below for use in the field trials. The iron was added as asolution of ferric sulfate including citric acid as a solubilizingligand.

PMIDA Fe:PMIDA Ratio Composition Formulation (wt %) (wt:wt) 539 ROUNDUPWEATHERMAX 0.06 No Fe Added 640 ROUNDUP WEATHERMAX 0.1 No Fe Added 922ROUNDUP WEATHERMAX 0.2 No Fe Added 740 ROUNDUP WEATHERMAX 0.3 No FeAdded 825 ROUNDUP WEATHERMAX 0.4 No Fe Added 739 ROUNDUP WEATHERMAX 0.1  4:1 734 ROUNDUP WEATHERMAX 0.2 1.5:1 770 ROUNDUP WEATHERMAX 0.2   2:1735 ROUNDUP WEATHERMAX 0.2 2.5:1 741 ROUNDUP WEATHERMAX 0.3 1.3:1 742ROUNDUP WEATHERMAX 0.4   1:1 736 ROUNDUP WEATHERMAX 0.4 1.5:1 737ROUNDUP WEATHERMAX 0.4   2:1 738 ROUNDUP WEATHERMAX 0.4 2.5:1 772ROUNDUP ORIGINALMAX 0.1 No Fe Added 807 ROUNDUP ORIGINALMAX 0.2 No FeAdded 775 ROUNDUP ORIGINALMAX 0.3 No Fe Added 902 ROUNDUP ORIGINALMAX0.4 No Fe Added 773 ROUNDUP ORIGINALMAX 0.1   6:1 743 ROUNDUPORIGINALMAX 0.2 1.5:1 831 ROUNDUP ORIGINALMAX 0.2   2:1 744 ROUNDUPORIGINALMAX 0.2 2.5:1 774 ROUNDUP ORIGINALMAX 0.2   3:1 776 ROUNDUPORIGINALMAX 0.3   2:1 745 ROUNDUP ORIGINALMAX 0.4 1.5:1 746 ROUNDUPORIGINALMAX 0.4   2:1 747 ROUNDUP ORIGINALMAX 0.4 2.5:1 817 ROUNDUPORIGINAL 0.4   2:1

A number of trials were applied relatively early in the season when thecotton was at the 5-6 leaf node stage and environmental conditions werecool and dry. There was no necrosis evident in any of these earlytrials. Later trials sprayed over 8-12 leaf node stage cotton with hottemperatures, high relative humidity, and abundant soil moisture showedhigh levels of necrosis with compositions containing no iron. Theanalyses that follow include only trials where necrosis was observed.T-test analyses combine data across trials and application rates.

Example 2A

This example investigated ROUNDUP WEATHERMAX-type compositions with setlevels of PMIDA (0.2% or 0.4%) and varying ratios of iron to PMIDA.Necrosis was evident in one trial and only at the higher level of PMIDA(composition 825, 0.4% PMIDA). All iron containing compositions with0.4% PMIDA showed significantly less necrosis than the standard (Table2A). Necrosis reduction was similar for all iron containing compositionsregardless of the iron to PMIDA ratio (1.5:1, 2:1, or 2.5:1). An exampleof the degree of necrosis reduction is shown in FIG. 5.

TABLE 2A T-Test Pairwise Mean Comparisons For 1 Experiment Compositionscompared to 825 as a Standard - Overall and by Species % DifferenceStandard Composition In Necrosis Significance n 825 736 6.1 ‡ 12 825 7376.1 ‡ 12 825 738 6.1 ‡ 12 ‡ Composition shows significantly lessnecrosis than Standard (p < 0.05)

Example 2B

This example investigated ROUNDUP WEATHERMAX-type compositions withconstant levels of iron and varying levels of PMIDA. Necrosis wasevident in two of the eight trials. Due to the low levels of necrosiswith compositions containing 0.1% and 0.2% PMIDA, differences betweencompositions with and without iron were not evident. When the level ofPMIDA was 0.3% or 0.4%, compositions containing iron showedsignificantly less necrosis than compositions with no iron (Table 2B).FIG. 6 graphically represents the data.

TABLE 2B T-Test Pairwise Mean Comparisons For 2 Experiments Compositionscompared to 640, 922, 740, or 825 as a Standard % Difference StandardComposition In Necrosis Significance N 640 739 1.3 − 24 922 770 1.9 − 24740 741 6.0 ‡ 24 825 742 11.1 + 24 − Composition can not bedistinguished from Standard (p ≧ 0.05) ‡ Composition shows significantlyless necrosis than Standard (p < 0.05) + Composition shows significantlyless necrosis than Standard (p < 0.01)

Example 2C

This example investigated the ability of iron to mitigate necrosis inROUNDUP ORIGINALMAX-type compositions with set levels of PMIDA (0.2 or0.4%) and varying ratios of iron to PMIDA (1.5:1, 2:1, or 2.5:1).Necrosis was evident in three of the eight trials. All compositionscontaining iron showed significantly less necrosis than the relevantstandards, composition 807 (0.2% PMIDA) and composition 902 (0.4% PMIDA)(Table 2C). The decrease in necrosis was similar for all ratios of ironto PMIDA (1.5:1, 2:1 or 2.5:1) and necrosis was essentially eliminated(FIG. 7).

TABLE 2C T-Test Pairwise Mean Comparisons For 3 Experiments Compositionscompared to 807 or 902 as a Standard % Difference Standard CompositionIn Necrosis Significance n 807 831 2.1 ‡ 35 807 744 2.3 + 36 807 7432.4 + 36 902 745 10.1 + 36 902 746 10.4 + 36 902 747 10.4 + 36 ‡Composition shows significantly less necrosis than Standard (p < 0.05) +Composition shows significantly less necrosis than Standard (p < 0.01)

Example 2D

This example investigated ROUNDUP ORIGINALMAX-type compositions withconstant levels of iron and varying levels of PMIDA. Necrosis wasevident in three of the eight trials. The lack of necrosis withcomposition 772 (0.1% PMIDA) resulted in no significant differences withcomposition 773 (Table 2D). The iron containing compositions with higherlevels of PMIDA all showed significantly less necrosis than theircorresponding compositions without iron. FIG. 8 graphically representsthe data

TABLE 2D T-Test Pairwise Mean Comparisons For 3 Experiments Compositionscompared to 772, 807, 775, or 902 as a Standard % Difference StandardComposition In Necrosis Significance n 772 773 0.2 − 36 807 774 4.7 † 36775 776 10.3 † 36 902 745 17.9 † 36 − Composition can not bedistinguished from Standard (p ≧ 0.05) † Composition is significantlyless efficacious than Standard (p < 0.01)

Example 2E

All compositions contained 0.4% PMIDA, except composition 539 (0.06%PMIDA), and varying levels of iron. Those compositions containing ironshowed significantly less necrosis than composition 902 (ROUNDUPORIGINALMAX, 0.4% PMIDA) and composition 825 (ROUNDUP WEATHERMAX, 0.4%PMIDA) (Table 2E). Composition 539, the 0.06% PMIDA and no ironcomposition, also was effective in minimizing necrosis. A graphicalrepresentation of the data is shown in FIG. 9.

TABLE 2E T-Test Pairwise Mean Comparisons For 5 Experiments Compositionscompared to 902 as a Standard % Difference Standard Composition InNecrosis Significance n 902 825 −1.4 ‡ 60 902 742 11.4 + 60 902 81712.0 + 60 902 737 12.4 + 60 902 745 13.4 + 60 902 539 13.9 + 60 902 74714.2 + 60 ‡ Composition shows significantly more necrosis than Standard(p < 0.01) + Composition shows significantly less necrosis than Standard(p < 0.01)

Example 3 Analytical Procedure

N-(phosphonomethyl)iminodiacetic acid (PMIDA) levels were determinedusing a high-pressure liquid chromatography (HPLC) procedure. Separationwas performed on a precolumn (5 μm, Zorbax SB-C18 Analytical GuardColumn, 4.6×12.5 mm) and analytical column (5 μm, Zorbax SAX-300, 150mm×4.6 mm ID) with an isocratic solvent system of 100 mM KH₂PO₄ with thepH adjusted to 2.0 with concentrated phosphoric acid or an alternativeisocratic solvent system of 54.4 g KH₂PO₄, 4 g concentrated sulfuricacid and 22 mL concentrated phosphoric acid diluted to 4 L with HPLCgrade water. Flow rate was 0.70 mL/min. Post-column reagent (3.2 mMCuSO₄, 0.70 mL/min) was added to the column eluate just prior to anin-line reaction coil [PTFE tubing, 8 ft.× 1/32 in. ID ( 1/16 in. OD)]installed before the UV detector which produced a copper-PMIDAchromophore that was quantified at 250 nm.

A stock solution of 0.2000 wt. % PMIDA was prepared in HPLC grade water.The working solutions of 0.0020, 0.0050, 0.0080, and 0.0100 wt. % PMIDAwere prepared by appropriate dilution of the stock solution in HPLCgrade water, were stored at 4° C. and replaced with fresh workingsolutions every 2 months. A calibration curve was constructed from theworking solutions for each set of samples analyzed. Samples wereprepared by weighing to four significant figures and diluted with HPLCgrade water to give a sample solution containing between 0.0020 to0.0100 wt. % PMIDA. For both the working solutions and the samplesolutions, 50 μL was injected in the chromatographic system.

First Isocratic Solvent System: The chromatogram for an iron-containingglyphosate formulation concentrate sample diluted 20 fold with deionizedwater is shown in FIG. 10. The concentration of PMIDA in the analyzedsample solution was 0.0021 wt. % PMIDA, which corresponded to aconcentration of 0.0437 wt. % PMIDA in the glyphosate formulationconcentrate.

Alternative Isocratic Solvent System: The chromatogram for aniron-containing formulation concentrate sample diluted 20 fold with HPLCgrade water is shown in FIG. 11. The concentration of PMIDA in theanalyzed sample solution was 0.0025 wt. % PMIDA, which corresponded to aconcentration of 0.0519 wt. % PMIDA in the glyphosate formulationconcentrate.

The analytical method set forth in this Example is particularlyadvantageous in that it can accurately assess PMIDA content of materialscontaining appreciable quantities of one or more metal ions such as ironused as a safening agent in accordance with the present invention.

In view of the above, it will be seen that the several objects of theinvention are achieved and other advantageous results attained.

As various changes could be made in the above methods without departingfrom the scope of the invention, it is intended that all mattercontained in the above description or shown in the accompanying drawingsshall be interpreted as illustrative and not in a limiting sense.

When introducing elements of the present invention or the preferredembodiments thereof, the articles “a”, “an”, “the”, and “said” areintended to mean that there are one or more of the elements. The terms“comprising”, “including,” and “having” are intended to be inclusive andmean that there may be additional elements other than the listedelements.

What is claimed:
 1. A method for selectively controlling weeds in afield containing a crop of transgenic glyphosate-tolerant cotton plantshaving increased glyphosate tolerance in vegetative and reproductivetissues, the method comprising: when at least five leaf nodes arepresent on a cotton plant of said crop, applying to foliage of said cropand weeds a sufficient amount of a herbicidal glyphosate formulationcomprising N-(phosphonomethyl)glycine or an agronomically acceptablesalt thereof to control growth of said weeds without incurringsignificant glyphosate-mediated reproductive injury to said plant ofsaid crop; and controlling the concentration ofN-(phosphonomethyl)iminodiacetic acid and salts thereof present in theherbicidal glyphosate formulation and the application rate of theherbicidal glyphosate formulation to said crop and weeds in said fieldsuch that the application rate of N-(phosphonomethyl)iminodiacetic acidand salts thereof is no more than about 2.5 g ofN-(phosphonomethyl)iminodiacetic acid equivalent/hectare so as to notinduce significant leaf necrosis in said cotton plants of said crop. 2.A method for selectively controlling weeds in a field containing a cropof transgenic glyphosate-tolerant cotton plants having increasedglyphosate tolerance in vegetative and reproductive tissues, the methodcomprising: when at least five leaf nodes are present on a cotton plantof said crop, applying to the foliage of said crop and weeds asufficient amount of a herbicidal glyphosate formulation to controlgrowth of said weeds without incurring significant glyphosate-mediatedreproductive injury to said plant of said crop, the herbicidalglyphosate formulation comprising N-(phosphonomethyl)glycine or anagronomically acceptable salt thereof, N-(phosphonomethyl)iminodiaceticacid or salt thereof and a safening agent in a concentration sufficientto inhibit significant leaf necrosis in said crop induced byN-(phosphonomethyl)iminodiacetic acid or salt thereof present in theherbicidal glyphosate formulation, wherein said safening agent isselected from the group consisting of metal ions, antioxidants,humectants, light absorbing compounds, and mixtures thereof.
 3. Themethod of claim 1 or 2 wherein the herbicidal glyphosate formulation isapplied to said crop and weeds in said field when at least onereproductive node is present on the plant of said crop.
 4. The method ofclaim 1 or 2 wherein the herbicidal glyphosate formulation is applied tosaid crop and weeds in said field when ten or more leaf nodes arepresent on the plant of said crop.
 5. The method of claim 1 or 2 whereinthe herbicidal glyphosate formulation is applied to said crop and weedsin said field up to and including layby of said crop of transgenicglyphosate-tolerant cotton plants.
 6. The method of claim 1 or 2 whereinthe herbicidal glyphosate formulation is applied to said crop and weedsin said field when six or more leaf nodes and no more than fourteen leafnodes are present on the plant of said crop.
 7. The method of claim 1 or2 wherein glyphosate-mediated reproductive injury to said plant of saidcrop is quantified by flower pollen shed and/or lint yield.
 8. Themethod of claim 7 wherein said plant of said crop exhibits a flowerpollen shed comparable to that of a transgenic glyphosate-tolerantcotton plant in the absence of foliar application of a herbicidalglyphosate formulation after the four leaf node stage.
 9. The method ofclaim 7 wherein said plant of said crop exhibits a lint yield comparableto that of a transgenic glyphosate-tolerant cotton plant in the absenceof foliar application of a herbicidal glyphosate formulation after thefour leaf node stage.
 10. The method of claim 1 or 2 wherein leafnecrosis in said crop is quantified by the area of necrotic lesions onthe surface of the leaves of said plants of said crop and whereinnecrotic lesions on the surface of the leaves of said plants of saidcrop on average account for no more than about 5% of the total leaf areaof said plants of said crop.
 11. The method of claim 2 wherein saidsafening agent inhibits significant leaf necrosis in said crop inducedby N-(phosphonomethyl)iminodiacetic acid or salt thereof present in theherbicidal glyphosate formulation by inhibiting buildup of phytotoxicfree radicals in said plants of said crop.
 12. The method of claim 2wherein said safening agent comprises a metal ion that is subject toformation of a complex or salt with N-(phosphonomethyl)iminodiaceticacid or an anion formed by deprotonation or partial deprotonationthereof, the formation of such complex or salt being effective toinhibit significant leaf necrosis in said crop of transgenicglyphosate-tolerant cotton plants induced byN-(phosphonomethyl)iminodiacetic acid or salt thereof present in saidherbicidal glyphosate formulation.
 13. The method of claim 12 whereinthe metal ion is polyvalent.
 14. The method of claim 12 wherein themetal ion is a transition metal ion.
 15. The method of claim 12 whereinthe metal ion is selected from the group consisting of aluminum,antimony, iron, chromium, nickel, manganese, cobalt, copper, zinc,vanadium, titanium, molybdenum, tin, barium and mixtures thereof. 16.The method of claim 15 wherein the metal ion is selected from the groupconsisting of aluminum, copper, iron, zinc and mixtures thereof.
 17. Themethod of claim 16 wherein the safening agent comprises a mixture ofiron and zinc metal ions or a mixture of iron and copper metal ions. 18.The method of claim 2 wherein the concentration ofN-(phosphonomethyl)iminodiacetic acid and salts thereof present in theherbicidal glyphosate formulation and the application rate of theherbicidal glyphosate formulation to said crop and weeds in said fieldis such that the application rate of N-(phosphonomethyl)iminodiaceticacid and salts thereof is greater than about 2.5 g ofN-(phosphonomethyl)iminodiacetic acid equivalent/hectare.
 19. The methodof claim 1 wherein the concentration of N-(phosphonomethyl)iminodiaceticacid and salts thereof present in the herbicidal glyphosate formulationand the application rate of the herbicidal glyphosate formulation tosaid crop and weeds in said field are controlled such that theapplication rate of N-(phosphonomethyl)iminodiacetic acid and saltsthereof is no more than about 1.5 g of N-(phosphonomethyl)iminodiaceticacid equivalent/hectare.
 20. The method of claim 1 or 2 wherein thegenome of the transgenic glyphosate-tolerant cotton plants comprises oneor more DNA molecules selected from the group consisting of SEQ ID NO:1,SEQ ID NO:2, SEQ ID NO:3, and SEQ ID NO:4; or the genome of thetransgenic glyphosate-tolerant cotton plants in a DNA amplificationmethod produces an amplicon comprising SEQ ID NO:1 or SEQ ID NO:2; orthe transgenic glyphosate-tolerant cotton plants comprise a glyphosatetolerant trait that is genetically linked to a complement of a markerpolynucleic acid, and the marker polynucleic acid molecule is homologousor complementary to a DNA molecule selected from the group consisting ofSEQ ID NO:1 and SEQ ID NO:2.
 21. The method of claim 1 or 2 wherein thecrop of transgenic glyphosate-tolerant cotton plants comprises cottonplants grown from seed of cotton event designated MON 88913 and havingrepresentative seed deposited with American Type Culture Collection(ATCC) with Accession No. PTA-4854 or glyphosate-tolerant progenythereof.
 22. The method of claim 1 or 2 wherein the herbicidalglyphosate formulation is applied to said crop and weeds in said fieldwhen six or more leaf nodes and no more than eighteen leaf nodes arepresent on the plant of said crop.
 23. The method of claim 1 or 2wherein the herbicidal glyphosate formulation is applied to said cropand weeds in said field when six or more leaf nodes and no more thantwenty leaf nodes are present on the plant of said crop.
 24. The methodof claim 19 wherein the concentration ofN-(phosphonomethyl)iminodiacetic acid and salts thereof present in theherbicidal glyphosate formulation and the application rate of theherbicidal glyphosate formulation to said crop and weeds in said fieldare controlled such that the application rate ofN-(phosphonomethyl)iminodiacetic acid and salts thereof is no more thanabout 1.2 g of N-(phosphonomethyl)iminodiacetic acid equivalent/hectare.25. The method of claim 24 wherein the concentration ofN-(phosphonomethyl)iminodiacetic acid and salts thereof present in theherbicidal glyphosate formulation and the application rate of theherbicidal glyphosate formulation to said crop and weeds in said fieldare controlled such that the application rate ofN-(phosphonomethyl)iminodiacetic acid and salts thereof is no more thanabout 1 g of N-(phosphonomethyl)iminodiacetic acid equivalent/hectare.26. The method of claim 25 wherein the concentration ofN-(phosphonomethyl)iminodiacetic acid and salts thereof present in theherbicidal glyphosate formulation and the application rate of theherbicidal glyphosate formulation to said crop and weeds in said fieldare controlled such that the application rate ofN-(phosphonomethyl)iminodiacetic acid and salts thereof is no more thanabout 0.7 g of N-(phosphonomethyl)iminodiacetic acid equivalent/hectare.27. The method of claim 26 wherein the concentration ofN-(phosphonomethyl)iminodiacetic acid and salts thereof present in theherbicidal glyphosate formulation and the application rate of theherbicidal glyphosate formulation to said crop and weeds in said fieldare controlled such that the application rate ofN-(phosphonomethyl)iminodiacetic acid and salts thereof is no more thanabout 0.5 g of N-(phosphonomethyl)iminodiacetic acid equivalent/hectare.28. The method of claim 27 wherein the concentration ofN-(phosphonomethyl)iminodiacetic acid and salts thereof present in theherbicidal glyphosate formulation and the application rate of theherbicidal glyphosate formulation to said crop and weeds in said fieldare controlled such that the application rate ofN-(phosphonomethyl)iminodiacetic acid and salts thereof is no more thanabout 0.25 g of N-(phosphonomethyl)iminodiacetic acidequivalent/hectare.
 29. The method of claim 2 wherein the safening agentcomprises an antioxidant.
 30. The method of claim 29 wherein theantioxidant is selected from the group consisting of hydroquinone,resorcinol, BHA, BHT, and mixtures thereof.
 31. The method of claim 29or 30 wherein the molar ratio of antioxidant toN-(phosphonomethyl)iminodiacetic acid equivalent is from about 50:1 toabout 1:1.
 32. The method of claim 2 wherein the safening agentcomprises a humectant.
 33. The method of claim 32 wherein the humectantis hygroscopic and substantially non-ionizable in water.
 34. The methodof claim 33 wherein the humectant comprises a polyhydroxy alcohol. 35.The method of claim 34 wherein the humectant is selected from the groupconsisting of sorbitol, xylitol, inositol, mannitol, pantothenol,glycerol, and derivatives and mixtures thereof.
 36. The method of anyone of claims 32 to 35 wherein the molar ratio of humectant toN-(phosphonomethyl)iminodiacetic acid equivalent is from about 250:1 toabout 1:1.
 37. The method of claim 2 wherein the safening agentcomprises a light absorbing compound.
 38. The method of claim 37 whereinthe light absorbing compound comprises a dye.
 39. The method of claim 38wherein the light absorbing compound comprises3-carboxy-5-hydroxy-1-psulfophenyl-4-p-sulfophenylazopyrazole trisodiumsalt.